Unique, long-term effects of nicotine on adolescent brain.
Open accessAbstract
Adolescence is a time of major plasticity of brain systems that regulate motivated behavior and cognition, and is also the age of peak onset of nicotine use. Although there has been a decline in teen use of cigarettes in recent years, there has been a huge increase in nicotine vaping. It is therefore critically important to understand the impact of nicotine on this critical phase of brain development. Animal studies have shown that nicotine has unique effects on adolescent brain. The goal of this review is therefore to systematically evaluate age- and sex-differences in the effects of nicotine on brain and behavior. Both acute and chronic effects of nicotine on brain biochemistry and behavior, particularly drug reward, aversion, cognition and emotion, are evaluated. Gaps in our current knowledge that need to be addressed are also highlighted. This review compares and integrates human and animals findings. Although there can be no experimental studies in humans to confirm similar behavioral effects of teen nicotine exposure, an emerging observational literature suggests similarities across species. Given the substantial evidence for long-term negative impact of adolescent nicotine exposure on brain and behavior, further longitudinal assessment of health outcomes in teen and young adult e-cigarette users is warranted.
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Claims the paper makes
60 of 142 cited sources checked · 31 supported · 0 flagged · accuracy not yet measured
- Premisecitation
Marketing of e-cigarettes to adolescents has been very effective.
“Marketing of e-cigarettes to adolescents has been very effective (Marynak et al., 2018)”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites Marynak et al., 2018 source
The Discussion reports that four in five U.S. youths were exposed to e-cigarette advertising in 2016 and notes an association between advertising exposure and e-cigarette use. It does not establish that marketing caused adolescents to use e-cigarettes or otherwise measure how effective the marketing was. (LLM, conf=0.84)
Experimental — accuracy not yet measured
- Findingcitation
Nearly 1 million of these students vape daily.
“Of these, nearly 1 million are vaping daily.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites Cullen et al., 2019 source
The table in the Discussion estimates 3.64 million current e-cigarette users among middle and high school students, but the paper defines current use as use on at least one day in the preceding 30 days. A search for daily or every-day vaping found no estimate of how many students vape daily, so the nearly 1 million figure cannot be verified from our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measured
- Premisecitation
Serotonin systems are uniquely sensitive to nicotine during adolescence.
“Serotonin systems are also uniquely sensitive to nicotine during adolescence (Slotkin & Seidler, 2009; Bang & Commons, 2011; Dao et al., 2011).”
Quote in the paperSubstantial claim2 of 3 sources checked - Interpretationcitation
The tolerance of adolescents to nicotine aversion may reflect late maturation of the medial habenula to lateral dorsal tegmental pathway that underlies nicotine aversion.
“This may reflect late maturation of the medial habenula to lateral dorsal tegmental pathway that underlies nicotine aversion (Wolfman et al., 2018).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Wolfman et al., 2018 source
- Premisecitation
Nicotine-induced neuronal activation, measured by immediate early gene expression, is enhanced during adolescence in several limbic regions, including nucleus accumbens shell, basolateral amygdala, VTA, and medial prefrontal cortex.
“Nicotine-induced neuronal activation, as measured by immediate early gene expression, is also enhanced during adolescence in several limbic regions, including nucleus accumbens shell, basolateral amygdala, VTA and medial prefrontal cortex (Schochet et al., 2005; Shram et al., 2007; Dao et al., 2011).”
Quote in the paperSubstantial claim1 of 3 sources checked- cites Schochet et al., 2005 source
- cites Shram et al., 2007 source
- cites Dao et al., 2011 source
The ‘Acute and Subchronic Nicotine Treatment Induces Age-dependent Neural Activation’ section reports greater nicotine-induced c-fos expression in adolescent rats’ nucleus accumbens shell and basolateral amygdala. It reports no significant acute nicotine effect in the prefrontal cortex, and the supplied passages do not establish comparable immediate-early-gene activation in the VTA. Those regions may be covered by the sentence’s other citations, but Dao et al. supports only part of the list. (LLM, conf=0.90)
Experimental — accuracy not yet measured
- Premisecitation
Electrophysiological studies show that VTA dopamine neurons are more sensitive to nicotine-induced synaptic plasticity in adolescents than in adults.
“Furthermore, electrophysiological studies have shown that VTA dopamine neurons are more sensitive to nicotine-induced synaptic plasticity in adolescents than adults (Placzek et al., 2009).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Placzek et al., 2009 source
- Premisecitation
Radioligand binding to α4β2* nAChRs in the VTA, striatum, and prefrontal cortex is higher in adolescents than in adults.
“Radioligand binding to α4β2* nAChRs in the VTA and in the striatum and prefrontal cortex, which are enriched in dopamine terminals, is also higher in adolescents than adults (Doura et al., 2008).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites Doura et al., 2008 source
- Interpretationcitation
Some of the increased drug intake in adolescents during intravenous self-administration may reflect elevated motor activity and non-specific increases in responding.
“Some of the increased drug intake in adolescents in intravenous self-administration tests may reflect elevated motor activity and non-specific increases in responding (Gellner et al., 2016).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites Gellner et al., 2016 source
- Premisecitation
Acute nicotine is less effective in adolescents than in adults at enhancing the context pre-exposure facilitation effect, a hippocampal-dependent learning paradigm.
“Acute nicotine is also less effective in adolescents than adults at enhancing the context pre-exposure facilitation effect, a hippocampal-dependent learning paradigm (Kutlu et al., 2016).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites Kutlu et al., 2016 source
- Premisecitation
Brief low-dose nicotine treatment during early adolescence (P28-31), but not adulthood, increases presynaptic markers of serotonin function in the forebrain.
“Brief treatment with low-dose nicotine during early adolescence (postnatal days (P) 28–31) but not adulthood, also increases presynaptic markers of serotonin function in the forebrain (Dao et al., 2011).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Dao et al., 2011 source
- Premisecitation
Clinical and preclinical literature indicates that adult females are more sensitive to stressors, including nicotine, than adult males.
“This is consistent with a substantial clinical and pre-clinical literature that indicates that female adults are more sensitive to stressors, including nicotine, than males (Torres & O’Dell, 2016).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites Torres & O’Dell, 2016 source
- Findingcitation
When adult males were pretreated with the kappa opioid receptor antagonist norbinaltorphimine to block this modulation, they self-administered the drug combination at the same high rate as adolescents.
“When adult males were pretreated with the kappa opioid receptor antagonist, norbinaltorphimine, to block this they self-administered the drug combination at the same high rate as adolescents (Lárraga et al., 2017).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Lárraga et al., 2017 source
The Figure 4 caption (page not available in our copy) reports that norBNI significantly increased ethanol-plus-nicotine reinforced responses in adult male rats; the discussion says it did not significantly affect adolescent males. Neither passage establishes that pretreated adults self-administered the combination at the same rate as adolescents, so that comparison is unsupported. (LLM, conf=0.82)
Experimental — accuracy not yet measured
- Findingcitation
Our animal studies show a unique interaction between nicotine and alcohol in adolescent male rats.
“Our animal studies have also shown a unique interaction of nicotine and alcohol in adolescent male rats (Lárraga et al., 2017).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Lárraga et al., 2017 source
- Premisecitation
Nicotine treatment during early adolescence increases later cocaine-induced locomotor sensitization.
“Nicotine treatment during early adolescence also increases subsequent cocaine-induced locomotor sensitization”
Quote in the paperSubstantial claim1 of 3 sources checked - Findingcitation
Mechanistic studies showed that the decreased response to the drug combination in adults reflected late maturation of an inhibitory kappa opioid receptor modulation.
“Mechanistic studies showed that the decreased response to the drug combination in adults reflected the late maturation of an inhibitory kappa opioid receptor modulation.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Lárraga et al., 2017 source
- Premisecitation
Some clinical studies of tobacco cessation in teenagers indicate that they may be especially sensitive to withdrawal, showing dependence symptoms soon after smoking initiation and before daily smoking habits are established.
“Some clinical studies of cessation of tobacco use in teenagers indicate that they may be especially sensitive to withdrawal, exhibiting symptoms of dependence soon after smoking initiation and before the establishment of daily smoking habits (DiFranza et al., 2007; Dierker & Mermelstein, 2010; Zhan et al., 2012).”
Quote in the paperNot a substantial claim2 of 3 sources checked- cites DiFranza et al., 2007 source
- cites Dierker & Mermelstein, 2010 source
The introductory passage labeled Abstract > Conclusions says that some adolescents experience nicotine-dependence symptoms soon after initiation, before daily smoking. The Discussion also reports withdrawal symptoms among novice smokers. This paper is a prospective study of smoking behavior, not a clinical cessation study, and it does not establish that teenagers are especially sensitive to withdrawal. (LLM, conf=0.86)
Experimental — accuracy not yet measured - cites Zhan et al., 2012 source
The results (p. 4) report dependence symptoms, including smoking to relieve restlessness and irritability, before daily smoking in some adolescents. The paper’s summary also says symptoms can develop soon after initiation. However, this is a prospective study of smoking and dependence, not a clinical cessation study, and it does not establish that teenagers are especially sensitive to withdrawal relative to another group. (LLM, conf=0.86)
Experimental — accuracy not yet measured
- Premisecitation
Animals treated with nicotine during early adolescence, but not late adolescence or adulthood, show enhanced rewarding effects of cocaine, methamphetamine, and morphine in adulthood as measured by conditioned place preference.
“Animals treated with nicotine during early adolescence, but not late adolescence or adulthood, have been found to have enhanced rewarding effects of cocaine, methamphetamine and morphine, as measured by conditioned place preference later in adulthood”
Quote in the paperSubstantial claim1 of 3 sources checked- cites McMillen et al., 2005 source
- cites Alajaji et al., 2016 source
- cites Kota et al., 2018 source
The Results (sections 3.1–3.2; page unavailable) show that early-adolescent nicotine exposure enhanced morphine conditioned place preference in adulthood, whereas late-adolescent or adult exposure did not. The Introduction and Discussion report enhanced adult responses to cocaine and methamphetamine after adolescent nicotine exposure, but do not establish that the same age comparison and conditioned-place-preference measure apply to those drugs. (LLM, conf=0.86)
Experimental — accuracy not yet measured
- Premisecitation
Teen e-cigarette use is associated with higher risk of later starting and continuing cigarette smoking.
“teen e-cigarette use is associated with greater risk for subsequent initiation and continuation of cigarette smoking”
Quote in the paperSubstantial claim2 of 2 sources checked- cites Soneji et al, 2017 source
The Abstract Results and Conclusions report an association between e-cigarette use and later cigarette-smoking initiation and past-30-day cigarette smoking. But the Methods (Statistical Analysis) specify that the later-smoking analysis involved people who were not current cigarette smokers at baseline; it does not establish that e-cigarette use was associated with continuing to smoke cigarettes among existing smokers. (LLM, conf=0.87)
Experimental — accuracy not yet measured - cites Kinnunen et al., 2019 source
- Premisecitation
Adolescent self-administration of nicotine or nicotine plus ethanol increases oral ethanol consumption in young adult male rats.
“self-administration of nicotine or nicotine + ethanol during adolescence leads to increased oral consumption of ethanol in young adult males”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Lárraga et al., 2017 source
- Premisecitation
Nicotine treatment during adolescence, but not adulthood, increases anxiety in later life.
“Nicotine treatment during adolescence, but not adulthood, increases anxiety in later life”
Quote in the paperSubstantial claim1 of 3 sources checked - Premisecitation
Nicotine pretreatment of adolescents, but not adults, increases the subsequent reinforcing effects of cocaine.
“nicotine pretreatment of adolescents, but not adults, increases the subsequent reinforcing effects of cocaine”
Quote in the paperSubstantial claim3 of 3 sources checked - Findingcitation
Adolescent nicotine increases cocaine self-administration through a critical role of microglia.
“we have further examined the mechanism by which adolescent nicotine increases cocaine self-administration, and have demonstrated a critical role for microglia”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Linker et al., 2020 source
- Findingcitation
The long-lasting enhancement of cocaine intake after adolescent nicotine can be blocked by co-administering a serotonin 5HT1A or dopamine D2 receptor antagonist during nicotine pretreatment.
“The long-lasting enhancement of cocaine intake can be blocked by co-administration of a serotonin 5HT1A or dopamine D2 receptor antagonist during nicotine pretreatment”
Quote in the paperSubstantial claim2 of 2 sources checked- cites Dao et al., 2011 source
The section on 5-HT1A receptors reports that an antagonist co-administered during adolescent nicotine pretreatment blocked enhanced cocaine self-administration at the initial test. The cocaine self-administration section separately shows that nicotine’s effect persisted for at least 10 days, but does not show antagonist blockade at that later time. The paper discusses a dopamine D2-like agonist, not blockade of cocaine intake by a D2 antagonist. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites Linker et al., 2020 source
The Results section on D2 receptors (Fig. 5b; page not given) reports that raclopride, a D2 antagonist administered during nicotine pretreatment, blocked the increase in cocaine responding in adolescent rats. The paper does not report the same result for a serotonin 5HT1A antagonist. Its Methods describe cocaine self-administration beginning the day after the four-day nicotine pretreatment, so this experiment also does not establish that the blocked enhancement was long-lasting. (LLM, conf=0.90)
Experimental — accuracy not yet measured
- Premisecitation
Adolescent nicotine treatment also increases methamphetamine and ethanol intake.
“A similar increase in methamphetamine and ethanol intake following adolescent nicotine treatment has also been seen”
Quote in the paperSubstantial claim2 of 2 sources checked- cites Dao et al., 2011 source
- cites Pipkin et al., 2014 source
The Discussion reports that low-dose adolescent nicotine exposure increased methamphetamine intake in adult male rats compared with saline exposure. Our copy does not report an increase in ethanol intake; the study examined methamphetamine self-administration. (LLM, conf=0.90)
Experimental — accuracy not yet measured
- Findingown data
This effect was not observed in females.
“This was not observed in females.”
Quote in the paperSubstantial claim - Findingreasoning
There is a notable discrepancy between human studies, in which teens are thought to be more sensitive to withdrawal than adults, and preclinical studies, which observe the opposite.
“There is a notable discrepancy between human studies, in which teens are thought to be more sensitive to withdrawal than adults, and preclinical studies where the opposite is observed.”
Quote in the paperNot a substantial claim - Interpretationreasoning
The evidence indicates that adolescent nicotine exposure has long-term negative effects on brain and behavior.
“Given the substantial evidence for long-term negative impact of adolescent nicotine exposure on brain and behavior”
Quote in the paperSubstantial claim- Rests on an assumption: Adolescent nicotine exposure causes long-term negative effects on brain and behavior in humans.
- Interpretationreasoning
Observational human studies suggest that the behavioral effects of adolescent nicotine exposure are similar across species.
“an emerging observational literature suggests similarities across species”
Quote in the paperSubstantial claim- Rests on an assumption: Findings from animal models of adolescent nicotine exposure can be generalized to humans.
- Rests on an assumption: Observational human studies can confirm that behavioral effects of adolescent nicotine exposure are similar across species.
- Premisenone given
Animal research indicates that nicotine exerts effects on the adolescent brain that differ from its effects in adults.
“Animal studies have shown that nicotine has unique effects on adolescent brain.”
Quote in the paperSubstantial claim - Premisecitation
In vitro rubidium efflux assays show that α4β2* nAChRs have higher functional activity in striatum and other brain regions in adolescents than in adults.
“In vitro rubidium efflux assays have shown α4β2* nAChRs to have higher functional activity in striatum and other brain regions in adolescents than adults (Britton et al., 2007; Kota et al., 2007).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation
Miller et al. (2019) found an age-related increase in nicotine-induced hypothermia in male mice, with adult mice most sensitive.
“Miller et al. (2019) found an age-related increase in nicotine-induced hypothermia in male mice, with adult mice being the most sensitive.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Miller et al. (2019) source
- Premisecitation
This finding is consistent with an earlier study that compared self-administration of nicotine with the tobacco constituent acetaldehyde across sex and age.
“This finding is consistent with an earlier study in which self-administration of nicotine with the tobacco constituent, acetaldehyde, was compared across sex and age (Park et al., 2007).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Park et al., 2007 source
- Premisecitation
Some studies find adolescent rodents less sensitive than adults to the behavioral effects of nicotine.
“Some studies have found adolescent rodents to be less sensitive than adults to the behavioral effects of nicotine.”
Quote in the paperNot a substantial claim - Premisecitation
Expression of nAChR binding and subunit mRNA varies greatly across development.
“Expression of nAChR binding and subunit mRNA is highly variable across development (Thorpe et al., 2020).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Thorpe et al., 2020 source
- Interpretationcitation
In other behavioral paradigms, acute nicotine treatment produces enhanced or unique effects in adolescents.
“In contrast, acute nicotine treatment induces enhanced or unique effects in adolescents in other behavioral paradigms.”
Quote in the paperNot a substantial claim - Premisereasoning
Increased sensitivity to lower nicotine doses is also seen in many of the conditioned place preference studies described above.
“This increased sensitivity to lower nicotine doses is also seen in many of the conditioned place preference studies described above.”
Quote in the paperNot a substantial claim - Premisecitation
Using drinking behavior to measure nicotine reward, mice show a peculiar vulnerability to oral self-administration of nicotine during early adolescence.
“Using drinking behavior to measure the rewarding effect of nicotine, mice have also been shown to have a peculiar vulnerability to oral self-administration of nicotine during early adolescence (Adriani et al., 2002).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Adriani et al., 2002 source
- Premisecitation
In vivo microdialysis confirms that nicotine induces greater dopamine release in the nucleus accumbens of adolescents than of adults.
“In vivo microdialysis has confirmed that nicotine induces greater release of dopamine in the nucleus accumbens of adolescents than adults (Corongiu et al., 2020).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Corongiu et al., 2020 source
- Premisenone given
Age differences in nicotine-induced locomotor behavior are independent of sex.
“These age differences in nicotine-induced locomotor behavior are independent of sex.”
Quote in the paperNot a substantial claim - Interpretationreasoning
Differences in nicotine behavioral effects between adolescents and adults cannot be explained by differences in drug clearance rate.
“Thus, differences in nicotine behavioral effects between adolescents and adults cannot be accounted for by differences in drug clearance rate.”
Quote in the paperSubstantial claim - Premisecitation
In the ventral tegmental area, expression of many nAChR subunits is higher in adolescents than in adults.
“In the ventral tegmental area (VTA), a limbic dopamine cell body region, expression of many nAChR subunits is higher in adolescents than in adults (Azam et al., 2007).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Azam et al., 2007 source
- Premisereasoning
When motor activity and non-specific responding are controlled for, adolescent males are sensitive to lower doses of nicotine than adults at low schedules of reinforcement.
“However, when this is controlled for, adolescent males are seen to be sensitive to lower doses of nicotine than adults at low schedules of reinforcement.”
Quote in the paperSubstantial claim - Premisecitation
Clinical data link teen smoking to use of other drugs, especially psychostimulants.
“Clinical data have shown a link between teen smoking and use of other drugs, particularly psychostimulants.”
Quote in the paperNot a substantial claim - Premisecitation
Co-administration of the KCC2 agonist CLP290 prevents elevated drinking after adolescent nicotine exposure.
“This elevated drinking following adolescent nicotine exposure could be prevented by co-administration of the KCC2 agonist, CLP290”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Thomas et al., 2018 source
- Interpretationcitation
Preclinical studies confirm a positive interaction between nicotine and psychostimulants, especially after adolescent nicotine exposure.
“Preclinical studies have confirmed a positive interaction of nicotine with psychostimulants, particularly following adolescent nicotine exposure.”
Quote in the paperSubstantial claim - Premisecitation
Abrupt cessation of tobacco use in dependent smokers produces withdrawal symptoms with both somatic and affective components.
“Abrupt cessation of tobacco use in dependent smokers results in withdrawal symptoms that include both somatic and affective components.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Hughes, 2007a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation
In most studies, male adolescents show less prominent somatic withdrawal symptoms than adults.
“In most studies, male adolescents have been found to exhibit less prominent somatic withdrawal symptoms than adults (O’Dell et al., 2006; Kota et al., 2007; Shram et al., 2008; Keeley et al., 2019)”
Quote in the paperNot a substantial claim0 of 3 sources checked - Premisecitation
In adolescents, smoking and e-cigarette use are associated with greater alcohol consumption.
“smoking and e-cigarette use is associated with greater alcohol consumption in adolescents”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Kristjansson et al., 2015 source
- Interpretationcitation
Adolescent nicotine exposure increases the rewarding effects of other abused drugs.
“Adolescent nicotine also leads to increased rewarding effects of other abused drugs.”
Quote in the paperSubstantial claim - Premisecitation
Affective withdrawal signs, measured by anxiety-like behaviors, increased brain reward threshold, conditioned place avoidance, and depressive-like behaviors, are generally lower in adolescent rats and mice of both sexes than in adults.
“Affective signs of withdrawal, as measured by anxiety-like behaviors on the elevated plus maze and open field, increased brain reward threshold, conditioned place avoidance, and depressive-like behaviors in the forced swim test, are also generally found to be lower in adolescent rats and mice of both sexes than adults (O’Dell et al., 2006, 2007; Kota et al., 2007, 2008; Shram et al., 2008; Iñiguez”
Quote in the paperSubstantial claim0 of 3 sources checked- cites O’Dell et al., 2006, 2007
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites Kota et al., 2007, 2008
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites Shram et al., 2008 source
- Premisecitation
Female adolescent mice have been reported to show increased physical withdrawal signs compared with adults.
“although female adolescent mice have been reported to show increased physical withdrawal signs as compared to adults (Kota et al., 2008).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Kota et al., 2008 source
- Premisecitation
Another study of self-reported dependence symptoms suggested similarities to tobacco dependence but with some unique indicators.
“whereas another study of self-reported dependence symptoms suggested there were similarities to tobacco dependence but with some unique indicators (Soule et al., 2020).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Soule et al., 2020 source
- Premisecitation
Nicotine withdrawal after chronic passive administration in animals produces a syndrome with somatic and affective components, including disrupted operant performance, avoidance behavior, weight gain, anxiety-like behaviors, decreased reward sensitivity, and opioid-like withdrawal behaviors.
“Nicotine withdrawal following chronic passive administration in animals results in a syndrome with both somatic and affective components, including disrupted operant performance, avoidance behavior, weight gain, anxiety-like behaviors, decreased reward sensitivity, and opioid-like withdrawal behaviors (Malin, 2001; Hughes, 2007b).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Malin, 2001 source
- cites Hughes, 2007b
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation
Passive nicotine exposure during adolescence, but not adulthood, increases later ethanol intake in adult animals.
“Passive exposure to nicotine during adolescence, but not adulthood, also leads to a subsequent increase in ethanol intake in adults”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Thomas et al., 2018 source
- Interpretationcitation
The overall reduction in withdrawal signs in adolescent rodents compared with adults may reflect resistance to decreased mesolimbic dopamine function.
“This overall reduction in withdrawal signs in adolescent rodents as compared to adults may reflect a resistance to decreased mesolimbic dopamine function (Natividad et al., 2010, 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Natividad et al., 2010, 2012
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation
Early onset of smoking is strongly related to alcohol dependence and problem use.
“there is a strong relationship between early onset of smoking and alcohol dependence and problem use”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Grant & Dawson, 1997 source
- Premisecitation
People who used tobacco before age 15 were more than 80 times more likely to use illegal drugs than those who did not.
“those who used tobacco before age 15 were more than 80x more likely to use illegal drugs than those who did not”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Lai et al., 2000 source
- Interpretationcitation
Adolescent nicotine exposure can induce long-term changes in brain and behavior.
“adolescent nicotine exposure can induce long-term changes in brain and behavior”
Quote in the paperSubstantial claim - Interpretationreasoning
Preclinical findings suggest that teen nicotine vaping may result in similar long-term deleterious effects.
“These preclinical findings suggest that teen nicotine vaping may result in similar long-term deleterious effects”
Quote in the paperSubstantial claim- Rests on an assumption: Animal models of adolescent nicotine exposure are informative about human adolescent nicotine effects, including vaping.
- Interpretationreasoning
Preclinical studies have consistently shown unique effects of nicotine on the adolescent brain.
“preclinical studies have consistently shown unique effects of nicotine on adolescent brain”
Quote in the paperSubstantial claim - Interpretationreasoning
Adolescent nicotine exposure may produce long-term vulnerability to stress, resulting in a negative emotional state.
“adolescent nicotine exposure may produce a long-term vulnerability to the adverse effects of stress, resulting in a negative emotional state”
Quote in the paperSubstantial claim - Premisecitation
There is a strong association between teen use of tobacco products and anxiety and depression.
“There is a strong association between teen use of tobacco products and anxiety and depression”
Quote in the paperNot a substantial claim0 of 3 sources checked - Premisecitation
Attentional deficits in animals treated with nicotine as adolescents are reversed by prefrontal cortex infusion of the mGluR2 agonist LY379268.
“attentional deficits in animals treated with nicotine as adolescents are reversed by prefrontal cortex infusion of the mGluR2 agonist, LY379268”
Quote in the paperSubstantial claim - Premisecitation
Animals treated with nicotine as adolescents and tested as adults show decreased context-induced freezing.
“Animals treated with nicotine as adolescents that were tested as adults showed decreased context-induced freezing”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Holliday and Gould, 2016
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites Holliday et al., 2016
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation
Adolescent nicotine induces profound and long-lasting neuronal and molecular alterations in regions critical for emotional regulation.
“adolescent nicotine induces profound and long-lasting neuronal and molecular alterations in regions that are critical for emotional regulation”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
Adult performance in an object learning task and a novel object test is decreased after adolescent nicotine treatment in females but not males.
“Adult performance in an object learning task and a novel object test were decreased following adolescent nicotine treatment of females, but not males”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Mateos et al., 2011 source
- May combine two claims. 47
- Classified as probably not a substantial claim. 4
- The quote only partly states this claim. 1
May combine two claims.
FindingcitationE-cigarette use was almost as prevalent among 10th graders, and 8th graders showed a 157% increase in 30-day e-cigarette use over the last two years.
“Use of e-cigarettes was almost as prevalent among 10th graders, and was particularly troubling among 8th graders who showed a 157% increase in 30-day e-cigarette use over the last two years.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites Miech et al., 2019 source
The ‘To the Editor’ results report increased nicotine vaping among both 10th- and 8th-graders from 2017 to 2018. They give an 8th-grade increase of 2.6 percentage points over one year, not a 157% increase over two years, and do not establish that use among 10th-graders was almost as prevalent as among 12th-graders. (LLM, conf=0.83)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
FindingcitationAbout 5 million students in grades 6-12 used e-cigarettes within the past 30 days, up from about 3.6 million in 2018.
“In absolute numbers, the National Youth Tobacco Survey shows that ~5 million students in grades 6–12 have tried e-cigarettes within the past 30 days, an increase from ~3.6 million in 2018 (Cullen et al., 2019).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites Cullen et al., 2019 source
The 2018 NYTS table (Discussion) estimates 3.64 million current e-cigarette users among middle and high school students, supporting the comparison figure. It estimates 4.92 million current users of any tobacco product—not e-cigarettes—and the paper covers data only through 2018, so it does not support the claimed increase to about 5 million e-cigarette users. (LLM, conf=0.88)
Experimental — accuracy not yet measured
May combine two claims.
FindingcitationIn 2019, 25.4% of 12th graders used e-cigarettes within the last 30 days, an increase of 131% from two years earlier.
“According to Monitoring the Future survey data (Miech et al., 2019), 25.4% of 12th graders in 2019 used e-cigarettes within the last thirty days, an increase of 131% from two years previously”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites Miech et al., 2019 source
The To the Editor section reports Monitoring the Future data showing an increase in nicotine vaping among 12th graders from 2017 to 2018. It does not report 2019 use, a 25.4% prevalence, or a 131% increase over two years; those specifics are not supported by this paper. (LLM, conf=0.88)
Experimental — accuracy not yet measured
May combine two claims.
PremisecitationIn recent years, cigarette use among teenagers has declined while nicotine vaping has increased substantially.
“Although there has been a decline in teen use of cigarettes in recent years, there has been a huge increase in nicotine vaping.”
Quote in the paperSubstantial claim2 of 2 sources checked- cites Cullen et al., 2019 source
The Abstract (page unavailable) reports decreased menthol-cigarette use and increased flavored e-cigarette use among high school tobacco-product users from 2014 to 2018. It does not establish a decline in cigarette use generally or a huge increase in nicotine vaping among teenagers; the reported high-school flavored e-cigarette measure rose from 65.1% to 67.8%, and the middle-school measure was comparable in 2014 and 2018. (LLM, conf=0.87)
Experimental — accuracy not yet measured - cites Miech et al., 2019 source
The To the Editor section reports a sharp increase in nicotine vaping from 2017 to 2018. It also says use of each of six other nicotine products declined in a sample of 12th-graders, but those declines were not statistically significant; it does not establish a broader, multi-year decline in cigarette use among teenagers. (LLM, conf=0.84)
Experimental — accuracy not yet measured
May combine two claims.
PremisecitationE-cigarettes were introduced to the US market in 2007 and are now the most commonly used tobacco product among teenagers.
“Although introduced as recently as 2007 to the US market, e-cigarettes are now the most commonly used tobacco product among teenagers (Miech et al., 2017; Wang et al., 2019).”
Quote in the paperNot a substantial claim2 of 2 sources checked- cites Miech et al., 2017 source
The Introduction reports rapid growth in e-cigarette use among U.S. students, and the Results say recent vaping was about 50% more prevalent than recent cigarette smoking in the study sample. Neither passage establishes that e-cigarettes were introduced to the U.S. market in 2007 or that they were the most commonly used tobacco product among teenagers overall. (LLM, conf=0.83)
Experimental — accuracy not yet measured - cites Wang et al., 2019 source
The Abstract (Results) and Results (Current Tobacco Product Use) identify e-cigarettes as the most commonly used tobacco product among U.S. middle and high school students in 2019. Our copy does not state that e-cigarettes entered the U.S. market in 2007; searches for that date and market introduction found no supporting passage. (LLM, conf=0.87)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationIn the United States, tobacco cigarette use has declined in recent years while e-cigarette use has increased exponentially.
“Whereas the use of tobacco cigarettes has declined in the United States within recent years, the use of electronic cigarettes (e-cigarettes) has increased exponentially (Cullen et al., 2019; Miech et al., 2019).”
Quote in the paperNot a substantial claim2 of 2 sources checked- cites Cullen et al., 2019 source
The Abstract (page unavailable) reports that, among U.S. high school tobacco-product users, menthol cigarette use decreased and flavored e-cigarette use increased during 2014–2018. It does not establish a decline in cigarette use or an exponential increase in e-cigarette use across the United States generally; the reported e-cigarette increase was from 65.1% to 67.8% in that subgroup. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites Miech et al., 2019 source
In “TO THE EDITOR” (page unavailable), the paper reports a sharp rise in nicotine vaping among U.S. adolescents from 2017 to 2018 and says use of six other nicotine products declined, though not significantly. It does not establish exponential growth or a decline in cigarette use across the U.S. population as a whole. (LLM, conf=0.88)
Experimental — accuracy not yet measured
May combine two claims.
PremisecitationE-cigarettes have been insufficiently regulated and have been readily available to minors in some states.
“To date there has been insufficient regulation of these potentially dangerous tobacco products and, as a result, they have been readily available to minors in some states (Paradise, 2014).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites Paradise, 2014 source
May combine two claims.
PremisecitationAdult female rats show less aversion to nicotine than adult males or ovariectomized females, suggesting that ovarian hormones protect against this effect.
“Adult female rats show less aversion to nicotine than do adult males or oviarectomized females, suggesting that ovarian hormones protect against this effect (Torres et al, 2009).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites Torres et al, 2009 source
May combine two claims.
PremisecitationNicotine acts through nicotinic cholinergic receptors, which are pentameric ligand-gated ion channels widely distributed throughout the brain.
“Nicotine mediates its effects via nicotinic cholinergic receptors (nAChRs), pentameric ligand-gated ion channels that are widely distributed throughout the brain (Dani, 2015; Zoli et al., 2015).”
Quote in the paperNot a substantial claim2 of 2 sources checkedMay combine two claims.
PremisecitationThis nicotine treatment does not affect presynaptic dopamine markers but increases the efficacy of striatal D2 dopamine receptors.
“Although presynaptic dopamine markers are not impacted by this nicotine treatment, there is an increase in the efficacy of striatal D2 dopamine receptors (Mojica et al., 2014; Linker et al., 2020).”
Quote in the paperSubstantial claim1 of 2 sources checked- cites Mojica et al., 2014 source
- cites Linker et al., 2020 source
The Results section on D2 receptors states that receptor signaling increases after adolescent nicotine exposure, supporting the D2-efficacy part of the claim. The paper does not establish that presynaptic dopamine markers are unaffected; its Results and Discussion instead report decreases in the presynaptic markers synaptophysin and VGlut2, which are not identified as dopamine markers. (LLM, conf=0.85)
Experimental — accuracy not yet measured
May combine two claims.
PremisecitationNicotine is metabolized faster in rodents during pre-adolescence (P23-25) than in adults, producing lower blood levels, but no pharmacokinetic differences are seen during the adolescent period starting at P28.
“Although nicotine is more rapidly metabolized in rodents during pre-adolescence (P23–25) than in adults, leading to lower blood levels, no pharmacokinetic differences have been seen during the adolescent period starting at P28 (Portugal et al., 2012; Ahsan et al., 2014; Craig et al., 2014; Arany et al., 2017).”
Quote in the paperSubstantial claim3 of 3 sources checked- cites Portugal et al., 2012 source
Results §3.4 finds no difference in plasma nicotine levels among pre-adolescent, adolescent, and adult mice after acute or chronic treatment; the Discussion likewise reports no age-related difference in nicotine metabolism. This contradicts the claimed faster metabolism and lower blood nicotine levels in pre-adolescents. The absence of a detected difference between adolescents and adults is supported, but Methods §2.1 places the adolescent group at PND 38 at the start of experiments, not P28. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites Ahsan et al., 2014 source
The Results section on blood nicotine levels reports concentrations after doses that produced place preference or self-administration, but does not compare nicotine metabolism or blood levels across ages. The Methods and Discussion likewise do not address faster metabolism at P23–25 or the absence of pharmacokinetic differences from P28; searches for those terms and age-related blood-level differences found no supporting passage. (LLM, conf=0.76)
Experimental — accuracy not yet measured - cites Craig et al., 2014 source
The Abstract and Results report lower plasma nicotine levels and faster nicotine clearance in early-adolescent rats at postnatal day 25 than in adults. The Discussion does not support the more specific claim that faster metabolism caused the lower levels; it points primarily to clearance and distribution and does not find faster conversion to cotinine. The paper compares day-25 rats with adults, so it does not establish that pharmacokinetic differences disappear starting at day 28. Page numbers were unavailable in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measured
May combine two claims.
PremisecitationnAChRs are expressed early in brain development and play critical maturational roles at many stages, including adolescence.
“nAChRs are expressed early in brain development and play critical maturational roles at many developmental stages, including adolescence (reviewed by Dwyer et al., 2009).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites Dwyer et al., 2009 source
May combine two claims.
PremisecitationAdolescent males show a strong anxiolytic response to nicotine that diminishes with age, whereas adolescent females show much lower anxiolytic or outright anxiogenic responses depending on the behavioral test.
“Adolescent males have been shown to have a strong anxiolytic response to nicotine treatment which diminishes with age, whereas adolescent females have much lower anxiolytic or outright anxiogenic responses depending on the behavioral test (Elliott et al., 2004; Cao et al., 2010).”
Quote in the paperSubstantial claim1 of 2 sources checkedMay combine two claims.
PremisecitationAdolescent mice showed learning enhancement only at the highest nicotine dose, whereas adult mice showed behavioral effects at lower doses.
“Whereas adolescent mice only showed learning enhancement at the highest nicotine dose, adult mice exhibited behavioral effects at lower nicotine doses.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites Kutlu et al., 2016 source
Probably not a substantial claim: may not pass S3 (load-bearing).
InterpretationcitationTobacco constituents, which have been shown to enhance reinstatement of nicotine-seeking behavior, may increase withdrawal signs.
“Alternatively, tobacco constituents, which have been shown to enhance reinstatement of nicotine seeking behavior (Costello et al., 2014; Cross et al., 2020), may increase withdrawal signs.”
Quote in the paperNot a substantial claim1 of 2 sources checkedMay combine two claims.
FindingcitationAlthough these findings may suggest that adolescent females find nicotine and tobacco more rewarding than males, recent data on middle and high school students show few sex differences in tobacco product use rates, with males showing slightly elevated consumption.
“Although these findings may suggest that adolescent females find nicotine and tobacco more rewarding than males, recent data on middle and high school students suggest few sex differences in rates of tobacco product use, with males showing slightly elevated consumption (Wang et al., 2019).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites Wang et al., 2019 source
May combine two claims.
PremisecitationResearch on e-cigarette withdrawal is limited, but recent analysis of the US Population Assessment of Tobacco and Health Survey and a clinical trial indicated that withdrawal symptoms were mild in never smokers.
“There is limited research on withdrawal from e-cigarettes, but recent analysis of the US Population Assessment of Tobacco and Health Survey and a clinical trial by the same investgators indicated that withdrawal symptoms were mild in never smokers (Hughes & Callas, 2019; Hughes et al., 2020)”
Quote in the paperNot a substantial claim1 of 2 sources checkedMay combine two claims.
PremisecitationTwo studies using an inhalation method for tobacco smoke or nicotine noted substantial physical withdrawal in adolescents, although adults were not included for comparison.
“Two studies in which an inhalation method for tobacco smoke or nicotine was used did note substantial physical withdrawal in adolescents, although adults were not included for comparison (de la Pena, 2015; Kallupi et al., 2019).”
Quote in the paperSubstantial claim1 of 2 sources checkedMay combine two claims.
PremisecitationAdolescent nicotine exposure increases later nicotine reward and reduces nicotine aversion in adult animals.
“Adolescent nicotine treatment increases subsequent nicotine reward and decreases aversion in adults”
Quote in the paperSubstantial claim3 of 3 sources checked- cites Adriani et al., 2003 source
The Results report that nicotine pretreatment during periadolescence increased nicotine self-administration in adult rats, and the Discussion interprets this as greater sensitivity to nicotine’s reinforcing effects. Our copy does not report reduced nicotine aversion; searches for aversion and aversive effects did not find support for that part of the claim. No page numbers were available in the indexed passages. (LLM, conf=0.86)
Experimental — accuracy not yet measured - cites Torres et al., 2008 source
The Discussion reports that adult rats exposed to nicotine during adolescence did not show the aversion seen at the highest dose in naïve adults. But it also says those rats did not show increased nicotine reward: their dose-response curve was relatively flat, and adolescent exposure did not facilitate conditioned place preference in adulthood. (LLM, conf=0.90)
Experimental — accuracy not yet measured - cites Kallupi et al., 2019 source
The Discussion (page unavailable) reports that high-dose adolescent nicotine-vapor exposure facilitated nicotine self-administration in adult rats. It suggests increased positive reinforcement as one possible explanation, but also offers withdrawal-related reinforcement; it does not establish increased nicotine reward or decreased nicotine aversion. (LLM, conf=0.88)
Experimental — accuracy not yet measured
May combine two claims. The quote only partly states this claim.
FindingcitationIn Sprague Dawley rats, once-daily low-dose nicotine (0.06 mg/kg, i.v.) for four days, intended to mimic early teen smoking, enhances subsequent reinforcing effects of cocaine, methamphetamine, and alcohol in adolescents but not adults of both sexes.
“we have used a paradigm in which Sprague Dawley rats are treated once daily for four days with a low dose of nicotine (0.06 mg/kg, i.v.), intended to mimic the early phase of teen smoking, and have shown this enhances subsequent reinforcing effects of cocaine, methamphetamine and alcohol”
Quote in the paperSubstantial claim1 of 2 sources checked- cites McQown et al., 2007
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites Dao et al., 2011 source
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
May combine two claims.
PremisecitationMicroglial activation selectively prunes glutamate synapses in the nucleus accumbens and basolateral amygdala and increases cocaine self-administration.
“Microglial activation then selectively prunes glutamate synapses in the nucleus accumbens and basolateral amygdala, and results in increased cocaine self-administration.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Linker et al., 2020 source
The Results section on synaptophysin reports a microglia-dependent decrease in a presynaptic marker in the nucleus accumbens after adolescent nicotine exposure; VGlut2 decreased while VGlut1 did not. The Results section on cocaine self-administration reports that suppressing or eliminating microglia blocked nicotine-induced increases in cocaine reinforcement. The paper does not show selective pruning of glutamate synapses in both the nucleus accumbens and basolateral amygdala: its synaptic-marker findings concern the nucleus accumbens, and decreased marker levels are not direct evidence of pruning. (LLM, conf=0.88)
Experimental — accuracy not yet measured
May combine two claims.
FindingcitationAdolescents who use flavorants are often unaware of their nicotine exposure; in one study, 40% of subjects with significant urinary cotinine reported using only nicotine-free products.
“Adolescents who use flavorants are also frequently unaware of their nicotine exposure, with 40% of subjects with significant urinary cotinine in a recent study reporting that they used only nicotine-free products (Boykan et al., 2019b).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Boykan et al., 2019b
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
May combine two claims.
FindingcitationAdolescents who used e-cigarettes with non-traditional flavors were more likely to continue vaping and to take more puffs per session six months later.
“Furthermore, adolescents who used e-cigarettes with non-traditional flavors are more likely to continue vaping and take more puffs per session six months later (Leventhal et al., 2019).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Leventhal et al., 2019 source
May combine two claims.
FindingcitationAdriani and colleagues found no sex differences in this effect, but most other studies have not compared sex and age differences within the same study to allow direct comparison of males and females.
“Whereas Adriani and colleagues found no sex differences in this effect, most other studies have not compared sex and age differences within the same study to allow a direct comparison of males and females.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn an intravenous self-administration paradigm, nicotine combined with alcohol is self-administered at much higher rates in male adolescents than in adults, and with much greater alcohol intake in adolescents than alcohol alone.
“Using an intravenous self-administration paradigm, we have shown that nicotine combined with alcohol is self-administered at much higher rates in male adolescents than adults, and with much greater alcohol intake in adolescents than that of alcohol alone (Figure 2A).”
Quote in the paperSubstantial claimMay combine two claims.
Findingnone givenThese withdrawal signs are routinely seen in adult rodents but not in adolescents.
“Although these withdrawal signs are routinely seen in adult rodents, this is not the case for adolescents.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationFlavorants can produce different patterns of nicotine delivery and reduce perceived risk.
“Flavorants can lead to different patterns of nicotine delivery and a decreased perception of risk (Voos et al., 2019; Jensenn and Boykan, 2019; Boccio et al., 2020).”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites Voos et al., 2019
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites Jensenn and Boykan, 2019
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites Boccio et al., 2020 source
May combine two claims.
PremisecitationAdolescents of both sexes are more sensitive than adults to the rewarding effects of nicotine in conditioned place preference tests, with some studies showing reward after a single drug-context pairing.
“Adolescents of both sexes are more sensitive than adults to the rewarding effects of nicotine, as shown in conditioned place preference tests (Vastola et al., 2002; Shram et al., 2006; Kota et al., 2007; Torres et al., 2008; Ahsan et al., 2014; Lenoir et al., 2015), with some studies demonstrating reward after a single pairing of drug and context (Belluzzi et al., 2004; Brielmaier et al., 2007).”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
InterpretationreasoningNicotine is a neurotoxicant that can produce unique and long-lasting negative behavioral effects in adolescents.
“However, as has been particularly highlighted in pre-clinical studies, described below, nicotine is a neurotoxicant that can produce unique and long-lasting negative behavioral effects in adolescents.”
Quote in the paperSubstantial claim- Rests on an assumption: Findings from animal models of adolescent nicotine exposure can be generalized to humans.
May combine two claims.
PremisecitationIn one recent study measuring reward by reduction in brain reward thresholds, adult males and females showed no sex difference in nicotine reward, whereas adolescent females (P40-59) were significantly more sensitive to nicotine reward than adolescent males.
“However, in one recent study in which reward was measured by reduction in brain reward thresholds, there was no sex difference in the rewarding effects of nicotine in adults, whereas adolescent females (P40–59) were significantly more sensitive to the rewarding effect of nicotine than their male counterparts (Xue et al., 2020).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Xue et al., 2020 source
May combine two claims.
PremisecitationNicotine-stimulated dopamine release from ventral striatal slices is age- and sex-dependent, highest in male rats during early adolescence (P30), with no significant age differences in females.
“Nicotine-stimulated dopamine release from ventral striatal slices shows complex age- and sex-dependence, being highest in male rats during early adolescence (postnatal day (P)30), with females showing no significant age differences (Azam et al., 2007).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Azam et al., 2007 source
May combine two claims.
PremisecitationNicotine inhibits locomotor activity in late adolescence and adulthood, but in early adolescence it either has no effect or stimulates motor activity.
“Whereas nicotine inhibits locomotor activity in late adolescence and adulthood, it either has no effect (Lopez et al., 2003; Belluzzi et al., 2004; Miller et al., 2019) or stimulates motor activity in early adolescence (Adriani et al., 2002; Cao et al., 2010).”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
InterpretationreasoningLow perceived health risk, appealing flavors, and minimal market regulation have created conditions for wide e-cigarette use among adolescents.
“The perceptions of low health risk, combined with the appeal of flavors and minimal market regulations, have created a climate for the wide use of e-cigarettes among adolescents.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationAdults of both sexes experience aversive effects from high doses of nicotine, whereas adolescents tolerate the drug well.
“Whereas adults of both sexes experience aversive effects of high doses of nicotine, adolescents tolerate the drug well (Adriani et al., 2002; Shram et al., 2006; Torres et al., 2008, 2009; Lenoir et al., 2015).”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
Interpretationnone givenMost studies show age differences in the acute in vivo effects of nicotine, but the pattern of these differences is not consistent.
“Whereas most studies have shown age differences in the acute in vivo effects of nicotine, there is no consistent pattern to these findings.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationEarly-adolescent DBA/2J mice were insensitive to nicotine-induced hypothermia while C57BL/6J mice were sensitive at that age; both strains became more sensitive as development progressed.
“Strain differences were observed in which early-adolescent mice of the DBA/2J strain were insensitive to nicotine-induced hypothermia, whereas C57BL/ 6J were sensitive at this age. However, both strains showed increased sensitivity to nicotine as development progressed.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Miller et al. (2019) source
May combine two claims.
PremisecitationLate-adolescent animals show the same inhibitory locomotor response to acute nicotine as adults but greater locomotor sensitization to repeated nicotine treatment.
“Although animals in late adolescence exhibit the same inhibitory locomotor response to acute nicotine as adults, they show greater locomotor sensitization to repeated nicotine treatment (Belluzzi et al., 2004).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Belluzzi et al., 2004 source
May combine two claims.
InterpretationcitationDespite one group arguing against a biological vulnerability of adolescents to nicotine, most studies show that adolescent rats readily acquire intravenous nicotine self-administration and have higher drug intake than adults.
“Although one group has argued against a biological vulnerability of adolescents to nicotine (Shram et al., 2008), the majority of studies have shown that adolescent rats readily acquire intravenous nicotine self-administration and have higher drug intake than adults (Chen et al., 2007; Levin et al. 2003, 2007; Natividad et al., 2013: Ahsan et al., 2014; Gellner et al., 2016).”
Quote in the paperNot a substantial claim0 of 3 sources checkedMay combine two claims.
PremisecitationStrain differences exist in adolescent physical withdrawal signs: Sprague Dawley rats of both sexes show significant withdrawal for two days after nicotine removal, whereas Long Evans rats show shortened (males) or non-existent (females) withdrawal.
“Strain differences have also been noted in adolescent physical withdrawal signs (Hamilton et al., 2010); whereas Sprague Dawley rats of both sexes were found to show significant withdrawal signs for two days after nicotine removal, Long Evans rats exhibit shortened (males) or non-existent (females) withdrawal.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Hamilton et al., 2010 source
May combine two claims.
PremisecitationBoth sexes found the nicotine-acetaldehyde combination highly rewarding during early adolescence (P27); this reinforcing effect diminished significantly in males at later ages (P34 and adult) but remained high in females.
“Whereas both sexes found the drug combination to be highly rewarding during early adolescence (P27), this initial reinforcing effect had significantly diminished in males at later ages (P34 and adult), whereas it remained high in females.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Park et al., 2007 source
May combine two claims.
PremisecitationAdolescent, but not adult, nicotine downregulates KCC2, shifts EGABA depolarizing, and inhibits ethanol-stimulated dopamine release.
“Adolescent, but not adult, nicotine downregulated the chloride channel, KCC2, causing a depolarizing shift in EGABA and resulting inhibition of ethanol-stimulated dopamine release.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Thomas et al., 2018 source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationSmoking and drinking are two of the earliest drug use behaviors in human teens, and many reports indicate a positive interaction between smoking and drinking in this age group.
“Smoking and drinking are two of the earliest drug use behaviors in human teens, and many reports indicate a positive interaction of smoking and drinking in this age group (Dani & Harris, 2005; Kristjansson et al., 2015).”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationAdult dependent smokers are more likely to be alcoholic than non-smokers, and most alcoholics smoke.
“Adult dependent smokers are also much more likely to be alcoholics than non-smokers, and the great majority of alcoholics smoke”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites DiFranza & Guerrera, 1990 source
- cites Falk et al., 2006
May combine two claims.
PremisecitationA recent study reported that teen e-cigarette users are more likely to report dependence signs and be daily users if they use high-nicotine-content pods such as Juul.
“A recent study has reported that teen e-cigarette users are more likely to report dependence signs and be daily users if they use high nicotine content pods, such as Juul (Boykan et al., 2019a).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Boykan et al., 2019a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
May combine two claims.
PremisecitationNicotine treatment of male adolescent rats increases impulsive behavior and decreases attention in adulthood, with no effect in rats treated as adults.
“Nicotine treatment of male adolescent rats resulted in increased impulsive behavior and decreased attention in adulthood, but had no effect on animals that are treated as adults”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Counotte et al., 2011 source
May combine two claims.
PremisecitationIn Lewis but not Fischer rats, adolescent nicotine treatment enhances cocaine conditioned place preference and potentiates dopamine response in the nucleus accumbens shell.
“only Lewis rats show enhancement of cocaine conditioned place preference and a concomitant potentiation of dopamine response in the nucleus accumbens shell following adolescent nicotine treatment”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Cadoni et al., 2019
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
May combine two claims.
PremisecitationThe enhancement of cocaine intake after adolescent nicotine pretreatment appears immediately and persists into adulthood, but is not seen for sucrose.
“The enhancement of cocaine intake is seen immediately following nicotine pretreatment and persists through adulthood, but is not seen for sucrose.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationAdolescent, but not adult, nicotine induces long-term social withdrawal and deficits in social cognition.
“adolescent, but not adult nicotine, induces long-term social withdrawal and deficits in social cognition”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Jobson et al., 2019 source
The paper relies on this without support.
Adolescence is a developmental period of high plasticity in brain systems that control motivated behavior and cognition.
“Adolescence is a time of major plasticity of brain systems that regulate motivated behavior and cognition”
The paper relies on this without support.
Adolescence is the period when nicotine use most commonly begins.
“is also the age of peak onset of nicotine use”
The paper relies on this without support.
Findings from animal models of adolescent nicotine exposure can be generalized to humans.
“This review compares and integrates human and animals findings.”
The paper relies on this without support.
The rodent adolescent period studied corresponds to human adolescence.
“no pharmacokinetic differences have been seen during the adolescent period starting at P28”
The paper relies on this without support.
Adolescent nicotine exposure causes long-term negative effects on brain and behavior in humans.
“Given the substantial evidence for long-term negative impact of adolescent nicotine exposure on brain and behavior”
The paper relies on this without support.
Observational human studies can confirm that behavioral effects of adolescent nicotine exposure are similar across species.
“an emerging observational literature suggests similarities across species”
The paper relies on this without support.
Animal models of adolescent nicotine exposure are informative about human adolescent nicotine effects, including vaping.
“Given ethical constraints on conducting experimental drug studies on human teens, this necessitates the use of animal studies.”
“These preclinical findings suggest that teen nicotine vaping may result in similar long-term deleterious effects”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
These findings align with a previous review, which suggested increased anxiety-related behaviour in adolescents, and extend findings by incorporating additional paradigms.
“These findings align with a previous review, which suggested increased anxiety-related behaviour in adolescents (Leslie, 2020), and extend findings by incorporating additional paradigms that measure different aspects of anxiety-related behaviour.”
From Age-dependent Effects of Tobacco Smoke and Nicotine on Cognition and the Brain: A Systematic Review of the Human and Animal Literature Comparing Adolescents and Adults. (2023) · cites this paper as Leslie, 2020
The review’s Emotional regulation section reports that nicotine treatment during adolescence increases anxiety in later life. That supports an association with adolescent nicotine exposure, but not the claim that anxiety-related behaviour is increased during adolescence. Its Acute nicotine effects section also describes an anxiolytic response in adolescent males. (LLM, conf=0.84)
Experimental — accuracy not yet measuredClinical studies have shown that nicotine exposure during adolescence, but not adulthood, is associated with subsequent increases in substance use (i.e., "gateway hypothesis").
“Clinical studies have shown that nicotine exposure during adolescence, but not adulthood, is associated with subsequent increases in substance use (i.e., “gateway hypothesis”) [6,7,105,145].”
From Nicotine on the developing brain. (2023) · cites this paper as [6]
In “Chronic effects of adolescent nicotine treatment > Drug reward” (page unavailable), the review reports clinical links between teen smoking and later use of other drugs, including cocaine. It does not report a clinical finding that adolescent exposure, but not adult exposure, predicts subsequent substance use; that age contrast comes from the animal studies it discusses. (LLM, conf=0.87)
Experimental — accuracy not yet measuredNicotine exposure during this highly plastic state induces long term changes in critical circuitry, maturation of monoamine systems, and behavior, including reward related behaviors.
“Nicotine exposure during this highly plastic state induces long term changes in critical circuitry, maturation of monoamine systems, and behavior, including reward related behaviors (see Fig. 3) [4,6,7].”
From Nicotine on the developing brain. (2023) · cites this paper as [6]
The Conclusions and “Drug reward” sections report long-term changes in brain circuitry and behavior after adolescent nicotine exposure, including increased reward from other drugs. The “Acute neurochemical effects on monoamine systems” and “Drug reward” sections describe changes in serotonin and dopamine signaling, but do not establish that nicotine changes the maturation of those systems. The evidence discussed is principally from animal studies; page numbers are unavailable in our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measuredAdolescent rodents show increased sensitivity to the locomotor activating and rewarding effects of nicotine, blunted withdrawal symptoms, and reduced aversion to high doses of nicotine, compared to adult counterparts.
“many studies have shown that adolescent rodents show an increased sensitivity to the locomotor activating and rewarding effects of nicotine, blunted withdrawal symptoms, and reduced aversion to high doses of nicotine, compared to adult counterparts.”
From Adolescent nicotine exposure and persistent neurocircuitry changes: unveiling lifelong psychiatric risks (2025) · cites this paper as [90]
The “Short-term behavioral effects” section supports greater nicotine reward and reduced aversion to high doses in adolescent rodents, while “Withdrawal syndrome” reports generally lower withdrawal signs than in adults. The locomotor claim needs an age qualifier: nicotine can stimulate activity in early adolescence, but inhibits it in late adolescence as it does in adulthood; late-adolescent rodents instead show greater sensitization after repeated treatment. Page numbers were not supplied. (LLM, conf=0.85)
Experimental — accuracy not yet measuredNicotine in adolescence increases later sensitivity to the rewarding effects of nicotine, while decreasing its aversive effects.
“Nicotine in adolescence has been shown to increase later sensitivity to the rewarding effects of nicotine, while decreasing its aversive effects; these studies have been thoroughly reviewed elsewhere, see: [90, 92]).”
From Adolescent nicotine exposure and persistent neurocircuitry changes: unveiling lifelong psychiatric risks (2025) · cites this paper as [90]
The ‘Acute nicotine effects in adolescents—Short-term behavioral effects’ section reports greater nicotine reward and less aversion in adolescent rodents than in adults. It does not establish that nicotine exposure during adolescence causes those responses later in life. The ‘Chronic effects—Drug reward’ section instead describes lasting increases in reward from other drugs. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Leslie's narrative review indicates increased nicotine reward sensitivity, dopamine release, and nAChR activity, but reduced nicotine aversion, during adolescence compared to adulthood.
“These narrative reviews by Leslie and colleagues point to increased nicotine reward sensitivity, dopamine release and activity of the nicotinic acetylcholine receptors (nAChRs), but reduced nicotine aversion during adolescence as compared to adulthood (Leslie, 2020).”
From Age-dependent Effects of Tobacco Smoke and Nicotine on Cognition and the Brain: A Systematic Review of the Human and Animal Literature Comparing Adolescents and Adults. (2023) · cites this paper as Leslie, 2020
Only two reviews have addressed how effects of tobacco smoke and nicotine on cognition and the brain may differ between adolescence and adulthood.
“only two reviews have addressed how effects may differ between adolescence and adulthood (Leslie, 2020; Yuan et al., 2015).”
From Age-dependent Effects of Tobacco Smoke and Nicotine on Cognition and the Brain: A Systematic Review of the Human and Animal Literature Comparing Adolescents and Adults. (2023) · cites this paper as Leslie, 2020
Nicotine produces reinforcing effects primarily through its action on the nicotinic acetylcholine receptor (nAchR) system, which is still immature during adolescence.
“Nicotine produces reinforcing effects primarily through its action on the nicotinic acetylcholine receptor (nAchR) system, which is still immature during adolescence [186].”
From Consequences of adolescent drug use (2023) · cites this paper as [186]
Microglial signaling is emerging as an important participant in long-term effects of ANE, and there are important differences in effects of ANE on adults versus adolescents.
“microglial signaling is emerging as an important participant in the long-term effects of ANE, and there are important differences in the effects of ANE on adults versus adolescents.”
From Consequences of adolescent drug use (2023) · cites this paper as [186]
While nicotine inhibits microglia activation in adults, the opposite effect has been found in adolescents.
“while nicotine inhibits microglia activation in adults, the opposite effect has been found in adolescents [186].”
From Consequences of adolescent drug use (2023) · cites this paper as [186]
Nicotine exposure during critical developmental periods disrupts neural development and often has long-lasting effects on associated behaviors.
“Nicotine exposure during critical developmental periods disrupts neural development, and often has long-lasting effects on associated behaviors [3–7].”
From Nicotine on the developing brain. (2023) · cites this paper as [6]
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BackgroundVital Signs: Tobacco Product Use Among Middle and High School Students — United States, 2011–2018
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BackgroundNicotine addiction and comorbidity with alcohol abuse and mental illness
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BackgroundEvidence for enhanced neurobehavioral vulnerability to nicotine during periadolescence in rats
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“Adolescent nicotine treatment increases subsequent nicotine reward and decreases aversion in adults (Adriani et al., 2003; Torres et al., 2008; Kallupi et al., 2019).”
BackgroundNicotine-induced conditioned place preference in adolescent and adult rats
Vastola, B. J., Douglas, L. A., Varlinskaya, E. I., & Spear, L. P. (2002) · Physiology & Behavior · doi:10.1016/s0031-9384(02)00818-1 · Cited by 251 · cited 1× · see citing works
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Impulse Control Disorders: Clinical Characteristics and Pharmacological Management
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ResultPsychiatric comorbidity in adolescent electronic and conventional cigarette use
Leventhal, A. M., Strong, D. R., Sussman, S. Y., Kirkpatrick, M. G., Unger, J. B., Barrington‐Trimis, J. L., & Audrain-McGovern, J. E. (2015) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2015.11.008 · Cited by 221 · cited 1× · see citing works
“There is a strong association between teen use of tobacco products and anxiety and depression (Patton et al., 1998; Jamner et al., 2003; McKenzie et al., 2010; Leventhal et al., 2016; Cho et al., 2018).”
BackgroundAdolescent-onset nicotine self-administration modeled in female rats
Levin, E. D., Rezvani, A. H., Montoya, D., Rose, J. E., & Swartzwelder, H. S. (2003) · Psychopharmacology · doi:10.1007/s00213-003-1486-y · Cited by 218 · see citing works
Peculiar vulnerability to nicotine oral self-administration in mice during early adolescence
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“Whereas nicotine inhibits locomotor activity in late adolescence and adulthood, it either has no effect (Lopez et al., 2003; Belluzzi et al., 2004; Miller et al., 2019) or stimulates motor activity in early adolescence (Adriani et al., 2002; Cao et al., 2010).”
BackgroundInfluentialAdolescent vaping and nicotine use in 2017-2018 - U.S. national estimates
Miech, R., Johnston, L., O’Malley, P. M., Bachman, J. G., & Patrick, M. E. (2019) · New England Journal of Medicine · doi:10.1056/nejmc1814130 · Cited by 213 · cited 3× · see citing works
“The teen vaping crisis Whereas the use of tobacco cigarettes has declined in the United States within recent years, the use of electronic cigarettes (e-cigarettes) has increased exponentially (Cullen et al., 2019; Miech et al., 2019).”
BackgroundMethodInfluentialThe association between cigarette smoking and drug abuse in the United States
Lai, S., Lai, H., Page, J. B., & McCoy, C. B. (2000) · Journal of Addictive Diseases · doi:10.1300/j069v19n04_02 · Cited by 212 · cited 1× · see citing works
“For example, one study showed that those who used tobacco before age 15 were more than 80x more likely to use illegal drugs than those who did not, with cocaine being the most widely used drug among teen cigarette smokers (Lai et al., 2000).”
BackgroundGender Differences in Binge Drinking: Prevalence, Predictors, and Consequences
Wilsnack, R. W., Wilsnack, S. C., Gmel, G. E., & Kantor, L. W. (2018) · Europe PMC (PubMed Central) · Cited by 210 · see citing works
Memory Function and the Hippocampus
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“The hippocampus is a brain region that is critical for memory formation and retrieval, and plays an important role in processing contextual information and spatial learning (Opitz, 2014).”
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Nicotine dependence and reward differ between adolescent and adult male mice
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“There is an increased number and activity of nAChRs in brain regions that are important for reward (Doura et al., 2007; Kota et al., 2007) , and an increase in nicotine-induced DA release in limbic regions of adolescent brain (Azam et al.”
BackgroundInfluentialShram, M. J., Funk, D., Li, Z., & Lê, A. D. (2006) · Psychopharmacology · doi:10.1007/s00213-006-0373-8 · Cited by 192 · cited 4× · see citing works
“…sexes are more sensitive than adults to the rewarding effects of nicotine, as shown in conditioned place preference tests (Vastola et al., 2002; Shram et al., 2006; Kota et al., 2007; Torres et al., 2008; Ahsan et al., 2014; Lenoir et al., 2015), with some studies demonstrating reward after a…”
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Flavored tobacco product use among middle and high school students—United States, 2014–2018
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“Somatic symptoms include bradycardia, insomnia, and gastrointestinal discomfort, whereas negative affective symptoms include anger, anxiety, craving, depression, difficulty concentrating, impatience, insomnia, and restlessness (Hughes, 2007a).”
BackgroundLechner, W. V., Janssen, T., Kahler, C. W., Audrain-McGovern, J. E., & Leventhal, A. M. (2016) · Preventive Medicine · doi:10.1016/j.ypmed.2016.12.034 · Cited by 170 · cited 1× · see citing works
“, 2008), there is substantial evidence for a bidirectional association between smoking/vaping and depression (Chaiton et al., 2009; Lechner et al., 2017; Esmaeelzadeh, 2018).”
BackgroundTORRES, O., TEJEDA, H., NATIVIDAD, L., & ODELL, L. (2008) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2008.05.009 · Cited by 169 · cited 4× · see citing works
“Adolescent nicotine treatment increases subsequent nicotine reward and decreases aversion in adults (Adriani et al., 2003; Torres et al., 2008; Kallupi et al., 2019).”
BackgroundInfluentialMalin, D. H. (2001) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(01)00699-2 · Cited by 167 · cited 1× · see citing works
“…passive administration in animals results in a syndrome with both somatic and affective components, including disrupted operant performance, avoidance behavior, weight gain, anxiety-like behaviors, decreased reward sensitivity, and opioid-like withdrawal behaviors (Malin, 2001; Hughes, 2007b).”
BackgroundNicotine Gateway Effects on Adolescent Substance Use
Ren, M., & Lotfipour, S. (2019) · Western Journal of Emergency Medicine · doi:10.5811/westjem.2019.7.41661 · Cited by 166 · see citing works
Stress is a principal factor that promotes tobacco use in females
Torres, O. V., & O'Dell, L. E. (2016) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2015.04.005 · Cited by 164 · see citing works
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“There is a strong association between teen use of tobacco products and anxiety and depression (Patton et al., 1998; Jamner et al., 2003; McKenzie et al., 2010; Leventhal et al., 2016; Cho et al., 2018).”
BackgroundSmoking to self-medicate attentional and emotional dysfunctions
Gehricke, J., Loughlin, S. E., Whalen, C. K., Potkin, S. G., Fallon, J., Jamner, L. D., Belluzzi, J. D., & Leslie, F. M. (2007) · Nicotine & Tobacco Research · doi:10.1080/14622200701685039 · Cited by 159 · cited 1× · see citing works
“Whereas many studies suggest that tobacco use is preceded by emotional dysregulation, and may be a form of self-medication (Gehricke et al., 2007; Weinstein et al., 2008), there is substantial evidence for a bidirectional association between smoking/vaping and depression (Chaiton et al.”
BackgroundSelf-citationNicotine exposure during adolescence induces a depression-like state in adulthood
Iñiguez, S. D., Warren, B. L., Parise, E. M., Alcantara, L. F., Schuh, B., Maffeo, M. L., Manojlovic, Z., & Bolaños-Guzmán, C. A. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2008.220 · Cited by 157 · see citing works
Collins, S. L., & Izenwasser, S. (2003) · Neuropharmacology · doi:10.1016/j.neuropharm.2003.09.024 · Cited by 154 · see citing works
Diminished nicotine withdrawal in adolescent rats: implications for vulnerability to addiction
O’Dell, L. E., Bruijnzeel, A. W., Smith, R. T., Parsons, L. H., Merves, M. L., Goldberger, B. A., Richardson, H. N., Koob, G. F., & Markou, A. (2006) · Psychopharmacology · doi:10.1007/s00213-006-0383-6 · Cited by 153 · see citing works
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“Adolescent males have been shown to have a strong anxiolytic response to nicotine treatment which diminishes with age, whereas adolescent females have much lower anxiolytic or outright anxiogenic responses depending on the behavioral test (Elliott et al., 2004; Cao et al., 2010).”
BackgroundLevin, E. D., Lawrence, S. S., Petro, A., Horton, K., Rezvani, A. H., Seidler, F. J., & Slotkin, T. A. (2007) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2007.02.002 · Cited by 147 · see citing works
Flavored E-cigarette use and progression of vaping in adolescents
Leventhal, A. M., Goldenson, N. I., Cho, J., Kirkpatrick, M. G., McConnell, R. S., Stone, M. D., Pang, R. D., Audrain-McGovern, J., & Barrington-Trimis, J. L. (2019) · Pediatrics · doi:10.1542/peds.2019-0789 · Cited by 142 · see citing works
Jacobsen, L. K., Pugh, K. R., Constable, R. T., Westerveld, M., & Mencl, W. E. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.02.014 · Cited by 140 · see citing works
Hanna, E. Z., Yi, H.-Y., Dufour, M. C., & Whitmore, C. C. (2001) · Journal of Substance Abuse · doi:10.1016/s0899-3289(01)00077-3 · Cited by 138 · cited 1× · see citing works
“Since most smokers begin before the age of 18 (Hanna et al., 2001; SAMHSA, 2011), it is critical that animal studies model the impact of adolescent nicotine exposure on alcohol intake and evaluate underlying mechanisms.”
BackgroundDevelopmental regulation of nicotinic acetylcholine receptors within midbrain dopamine neurons
Azam, L., Chen, Y., & Leslie, F. M. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2006.11.011 · Cited by 138 · cited 4× · see citing works
“Nicotine-stimulated dopamine release from ventral striatal slices shows complex age- and sex-dependence, being highest in male rats during early adolescence (postnatal day (P)30), with females showing no significant age differences (Azam et al., 2007).”
BackgroundInfluentialSelf-citationLasting synaptic changes underlie attention deficits caused by nicotine exposure during adolescence
Counotte, D. S., Goriounova, N. A., Li, K. W., Loos, M., van der Schors, R. C., Schetters, D., Schoffelmeer, A. N. M., Smit, A. B., Mansvelder, H. D., Pattij, T., et al. (2011) · Nature Neuroscience · doi:10.1038/nn.2770 · Cited by 132 · cited 3× · see citing works
“Cognitive performance has also been shown to be influenced negatively by adolescent nicotine exposure in animal studies (Schochet et al., 2005; 2008; Counotte et al., 2011).”
BackgroundThe Impact of Cigarette Smoking on Stimulant Addiction
Weinberger, A. H., & Sofuoglu, M. (2009) · The American Journal of Drug and Alcohol Abuse · doi:10.1080/00952990802326280 · Cited by 130 · see citing works
Doura, M. B., Gold, A. B., Keller, A. B., & Perry, D. C. (2008) · Brain Research · doi:10.1016/j.brainres.2008.03.056 · Cited by 129 · cited 1× · see citing works
“Radioligand binding to α4β2* nAChRs in the VTA and in the striatum and prefrontal cortex, which are enriched in dopamine terminals, is also higher in adolescents than adults (Doura et al., 2008).”
BackgroundLambert, N. M., McLeod, M., & Schenk, S. (2006) · Addiction · doi:10.1111/j.1360-0443.2006.01408.x · Cited by 123 · cited 1× · see citing works
“Furthermore, those who were regular smokers were more likely to ‘like’ or ‘want’ cocaine when they first tried it, responses that are significant predictors of dependence and lifetime cocaine use (Lambert et al., 2006).”
BackgroundMarynak, K., Gentzke, A., Wang, T. W., Neff, L., & King, B. A. (2018) · MMWR. Morbidity and Mortality Weekly Report · doi:10.15585/mmwr.mm6710a3 · Cited by 122 · cited 1× · see citing works
“Marketing of ecigarettes to adolescents has been very effective (Marynak et al., 2018), and manufacturers offer a wide selection of flavors that appeal to youth.”
BackgroundCannon, D. M., Klaver, J. M., Peck, S. A., Rallis, D., Erickson, K., & Drevets, W. C. (2008) · Neuropsychopharmacology · doi:10.1038/npp.2008.194 · Cited by 119 · cited 1× · see citing works
“Clinical studies have previously shown that striatal levels of the D1 receptor are negatively associated with major depression, particularly in those with anger attacks (Dougherty et al., 2006; Cannon et al., 2009).”
BackgroundLow dose nicotine treatment during early adolescence increases subsequent cocaine reward
McQuown, S. C., Belluzzi, J. D., & Leslie, F. M. (2007) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2006.10.012 · Cited by 117 · cited 1× · see citing works
“Other studies, using the self-administration procedure, have shown that nicotine pretreatment of adolescents, but not adults, increases the subsequent reinforcing effects of cocaine (McQuown et al., 2007; Dao et al., 2011; Reed & Izenwasser, 2017; Dickson et al., 2014; Linker et al., 2020), but see (Levin et al.”
ResultSelf-citationAcquisition of nicotine self-administration in adolescent rats given prolonged access to the drug
Chen, H., Matta, S. G., & Sharp, B. M. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301135 · Cited by 112 · cited 1× · see citing works
“, 2008), the majority of studies have shown that adolescent rats readily acquire intravenous nicotine self-administration and have higher drug intake than adults (Chen et al., 2007; Levin et al. 2003, 2007; Natividad et al., 2013: Ahsan et al., 2014; Gellner et al., 2016).”
BackgroundTorres, O. V., Natividad, L. A., Tejeda, H. A., Van Weelden, S. A., & O’Dell, L. E. (2009) · Psychopharmacology · doi:10.1007/s00213-009-1607-3 · Cited by 110 · cited 2× · see citing works
“Whereas adults of both sexes experience aversive effects of high doses of nicotine, adolescents tolerate the drug well (Adriani et al., 2002; Shram et al., 2006; Torres et al., 2008, 2009; Lenoir et al., 2015).”
BackgroundLozier, M., Wallace, B., Anderson, K. N., Ellington, S., Jones, C. M., Rose, D. A., Baldwin, G. T., King, B. A., Briss, P. A., Mikosz, C. A., et al. (2019) · MMWR Morbidity and Mortality Weekly Report · doi:10.15585/mmwr.mm6849e1 · Cited by 110 · see citing works
Mateos, B., Borcel, E., Loriga, R., Luesu, W., Bini, V, Llorente, R., Castelli, M., & Viveros, M.-P. (2011) · Journal of Psychopharmacology · doi:10.1177/0269881110370503 · Cited by 108 · cited 1× · see citing works
“Adult performance in an object learning task and a novel object test were decreased following adolescent nicotine treatment of females, but not males (Mateos et al., 2011).”
BackgroundKristjansson, A. L., Mann, M. J., & Sigfusdottir, I. D. (2015) · Journal of Adolescent Health · doi:10.1016/j.jadohealth.2015.07.014 · Cited by 104 · cited 2× · see citing works
“Smoking and drinking are two of the earliest drug use behaviors in human teens, and many reports indicate a positive interaction of smoking and drinking in this age group (Dani & Harris, 2005; Kristjansson et al., 2015).”
BackgroundDelfino, R. J., Jamner, L. D., & Whalen, C. K. (2001) · Nicotine & Tobacco Research · doi:10.1080/14622200110050466 · Cited by 103 · cited 1× · see citing works
“This is an important area for further research, given human findings of sex differences in the relationship between smoking urges and mood states (Delfino et al., 2001).”
BackgroundAdolescent neurodevelopment and substance use: receptor expression and behavioral consequences
Thorpe, H. H. A., Hamidullah, S., Jenkins, B. W., & Khokhar, J. Y. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.107431 · Cited by 97 · cited 1× · see citing works
“Expression of nAChR binding and subunit mRNA is highly variable across development (Thorpe et al., 2020).”
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Mood variability and cigarette smoking escalation among adolescents.
Weinstein, S. M., Mermelstein, R. J., Shiffman, S. S., & Flay, B. R. (2008) · Psychology of Addictive Behaviors · doi:10.1037/0893-164x.22.4.504 · Cited by 93 · cited 1× · see citing works
“Whereas many studies suggest that tobacco use is preceded by emotional dysregulation, and may be a form of self-medication (Gehricke et al., 2007; Weinstein et al., 2008), there is substantial evidence for a bidirectional association between smoking/vaping and depression (Chaiton et al.”
BackgroundSchochet, T. L., Kelley, A. E., & Landry, C. F. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.05.057 · Cited by 93 · cited 2× · see citing works
“Cognitive performance has also been shown to be influenced negatively by adolescent nicotine exposure in animal studies (Schochet et al., 2005; 2008; Counotte et al., 2011).”
BackgrounddeBry, S., & Tiffany, S. (2008) · Nicotine & Tobacco Research · doi:10.1080/14622200701767811 · Cited by 92 · see citing works
Brielmaier, J. M., McDonald, C. G., & Smith, R. F. (2007) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2006.09.023 · Cited by 90 · cited 1× · see citing works
“, 2015), with some studies demonstrating reward after a single pairing of drug and context (Belluzzi et al., 2004; Brielmaier et al., 2007).”
BackgroundIncreased anxiety-like behavior in adult rats exposed to nicotine as adolescents
Slawecki, C. (2003) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(03)00093-5 · Cited by 87 · cited 1× · see citing works
“Nicotine treatment during adolescence, but not adulthood, increases anxiety in later life, as shown by elevated plus maze, time spent in the light side of a box, or time spent in the center zone of an open field (Slawecki et al., 2003; Smith et al., 2006; Iñiguez et al., 2009; Holliday et al., 2016; Jobson et al., 201…”
BackgroundFractalkine/CX3CR1 is involved in the cross-talk between neuron and glia in neurological diseases.
Luo, P., Chu, S.-F., Zhang, Z., Xia, C.-Y., & Chen, N.-H. (2019) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2018.11.017 · Cited by 85 · cited 1× · see citing works
“This immune response in adolescents is induced by nicotine via activation of D2 receptors, and a resulting neuronal release of the fractalkine signaling ligand, CXRCL1, which binds to microglial CX3CR1 receptors to regulate synaptic pruning (Figure 3; Luo et al., 2019).”
BackgroundO’Dell, L. E., Torres, O. V., Natividad, L. A., & Tejeda, H. A. (2006) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2006.11.003 · Cited by 84 · see citing works
Evidence of Nicotine Dependence in Adolescents Who Use Juul and Similar Pod Devices
Boykan, R., Goniewicz, M. L., & Messina, C. R. (2019) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph16122135 · Cited by 83 · cited 6× · see citing works
“, 2019), it should be noted that Juul and other vape pod systems result in adolescent exposure to high doses of nicotine and subsequent dependence (Goniewicz et al., 2018; Boykan et al., 2019).”
BackgroundInfluentialSelf-Reported Use of Tobacco, E-cigarettes, and Marijuana Versus Urinary Biomarkers
Boykan, R., Messina, C. R., Chateau, G., Eliscu, A. H., Tolentino, J., & Goniewicz, M. L. (2019) · PEDIATRICS · doi:10.1542/peds.2018-3531 · Cited by 82 · see citing works
Nicotine aversion is mediated by GABAergic interpeduncular nucleus inputs to laterodorsal tegmentum
Wolfman, S. L., Gill, D. F., Bogdanic, F., Long, K., Al-Hasani, R., McCall, J. G., Bruchas, M. R., & McGehee, D. S. (2018) · Nature Communications · doi:10.1038/s41467-018-04654-2 · Cited by 81 · see citing works
Nicotine alters limbic function in adolescent rat by a 5-HT1A receptor mechanism
Dao, J. M., McQuown, S. C., Loughlin, S. E., Belluzzi, J. D., & Leslie, F. M. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.8 · Cited by 79 · cited 10× · see citing works
“), intended to mimic the early phase of teen smoking, and have shown this enhances subsequent reinforcing effects of cocaine, methamphetamine and alcohol (McQown et al., 2007; Dao et al., 2011) in adolescents but not adults of both sexes.”
BackgroundResultInfluentialSelf-citationDevelopmental effects of acute, chronic, and withdrawal from chronic nicotine on fear conditioning
Portugal, G. S., Wilkinson, D. S., Turner, J. R., Blendy, J. A., & Gould, T. J. (2012) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2012.04.003 · Cited by 79 · cited 1× · see citing works
“Although nicotine is more rapidly metabolized in rodents during pre-adolescence (P23–25) than in adults, leading to lower blood levels, no pharmacokinetic differences have been seen during the adolescent period starting at P28 (Portugal et al., 2012; Ahsan et al., 2014; Craig et al., 2014; Arany et al., 2017).”
BackgroundComparison of the reinforcing properties of nicotine and cigarette smoke extract in rats
Costello, M. R., Reynaga, D. D., Mojica, C. Y., Zaveri, N. T., Belluzzi, J. D., & Leslie, F. M. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.31 · Cited by 78 · cited 1× · see citing works
“Alternatively, tobacco constituents, which have been shown to enhance reinstatement of nicotine seeking behavior (Costello et al., 2014; Cross et al., 2020), may increase withdrawal signs.”
BackgroundSelf-citationMicroglial activation increases cocaine self-administration following adolescent nicotine exposure
Linker, K. E., Gad, M., Tawadrous, P., Cano, M., Green, K. N., Wood, M. A., & Leslie, F. M. (2020) · Nature Communications · doi:10.1038/s41467-019-14173-3 · Cited by 77 · cited 5× · see citing works
“Although presynaptic dopamine markers are not impacted by this nicotine treatment, there is an increase in the efficacy of striatal D2 dopamine receptors (Mojica et al., 2014; Linker et al., 2020).”
BackgroundResultInfluentialSelf-citationTorres, O. V., Gentil, L. G., Natividad, L. A., Carcoba, L. M., & O’Dell, L. E. (2013) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2013.00038 · Cited by 76 · cited 1× · see citing works
“Affective signs of withdrawal, as measured by anxiety-like behaviors on the elevated plus maze and open field, increased brain reward threshold, conditioned place avoidance, and depressive-like behaviors in the forced swim test, are also generally found to be lower in adolescent rats and mice of both sexes than adults…”
BackgroundAssociation of Anhedonia With Adolescent Smoking Susceptibility and Initiation
Stone, M. D., Audrain-McGovern, J. E., & Leventhal, A. M. (2017) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntw177 · Cited by 73 · cited 1× · see citing works
“Other predictors of teen and young adult smoking include anhedonia, aggression, low hedonic capacity and lower distress tolerance (Roberts et al., 2010; Audrain-McGovern et al., 2012; Trujillo et al., 2016; Stone et al., 2017; Trucco et al., 2018).”
BackgroundAge-dependent differences in nicotine reward and withdrawal in female mice
Kota, D., Martin, B. R., & Damaj, M. I. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1117-8 · Cited by 72 · see citing works
Roberts, S. J., Glod, C. A., Kim, R., & Hounchell, J. (2010) · Journal of the American Academy of Nurse Practitioners · doi:10.1111/j.1745-7599.2010.00521.x · Cited by 71 · cited 1× · see citing works
“Other predictors of teen and young adult smoking include anhedonia, aggression, low hedonic capacity and lower distress tolerance (Roberts et al., 2010; Audrain-McGovern et al., 2012; Trujillo et al., 2016; Stone et al., 2017; Trucco et al., 2018).”
BackgroundSMITH, L., MCDONALD, C., BERGSTROM, H., BRIELMAIER, J., EPPOLITO, A., WHEELER, T., FALCO, A., & SMITH, R. (2006) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2006.07.014 · Cited by 70 · see citing works
Periadolescent nicotine exposure causes heterologous sensitization to cocaine reinforcement
McMillen, B. A., Davis, B. J., Williams, H. L., & Soderstrom, K. (2005) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2005.01.002 · Cited by 66 · cited 1× · see citing works
“Animals treated with nicotine during early adolescence, but not late adolescence or adulthood, have been found to have enhanced rewarding effects of cocaine, methamphetamine and morphine, as measured by conditioned place preference later in adulthood (McMillen et al., 2005; Alajaji et al., 2016; Kota et al., 2018; Cad…”
BackgroundPeriadolescent Nicotine Exposure Reduces Cocaine Reward in Adult Mice
Kelley, B. M., & Middaugh, L. D. (1999) · Journal of Addictive Diseases · doi:10.1300/j069v18n03_04 · Cited by 65 · see citing works
Dougherty, D. D., Bonab, A. A., Ottowitz, W. E., Livni, E., Alpert, N. M., Rauch, S. L., D, M. F. M., & Fischman, A. J. (2006) · Depression and Anxiety · doi:10.1002/da.20168 · Cited by 64 · see citing works
Shram, M. J., Funk, D., Li, Z., & Lê, A. D. (2007) · Neuroscience Letters · doi:10.1016/j.neulet.2007.03.034 · Cited by 64 · cited 1× · see citing works
“Nicotine-induced neuronal activation, as measured by immediate early gene expression, is also enhanced during adolescence in several limbic regions, including nucleus accumbens shell, basolateral amygdala, VTA and medial prefrontal cortex (Schochet et al., 2005; Shram et al., 2007; Dao et al., 2011).”
BackgroundNatividad, L. A., Tejeda, H. A., Torres, O. V., & O'dell, L. E. (2010) · Synapse · doi:10.1002/syn.20713 · Cited by 64 · see citing works
Slawecki, C. J., Thorsell, A. K., Khoury, A. E., Mathé, A. A., & Ehlers, C. L. (2005) · Neuropeptides · doi:10.1016/j.npep.2005.06.002 · Cited by 64 · see citing works
Jobson, C. L. M., Renard, J., Szkudlarek, H., Rosen, L. G., Pereira, B., Wright, D. J., Rushlow, W., & Laviolette, S. R. (2019) · Cerebral Cortex · doi:10.1093/cercor/bhy179 · Cited by 64 · cited 5× · see citing works
“Mechanistic analyses have shown that adolescent nicotine induces profound and long-lasting neuronal and molecular alterations in regions that are critical for emotional regulation (Slawecki et al., 2005; Holliday et al., 2016; Jobson et al., 2019).”
BackgroundInfluentialNeurochemical alterations produced by daily nicotine exposure in periadolescent vs. adult male rats
Collins, S. L., Wade, D., Ledon, J., & Izenwasser, S. (2004) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2004.08.039 · Cited by 62 · cited 1× · see citing works
“This effect may be specific to males, however, since adolescent nicotine-induced enhancement of cocaine- and amphetamine-induced locomotor sensitization was not seen in female mice (Collins & Izenwasser, 2004; Collins et al., 2004).”
BackgroundNicotinic modulation of hippocampal cell signaling and associated effects on learning and memory
Kutlu, M. G., & Gould, T. J. (2015) · Physiology & Behavior · doi:10.1016/j.physbeh.2015.12.008 · Cited by 62 · see citing works
Age dependent nicotinic influences over dopamine neuron synaptic plasticity
Placzek, A. N., Zhang, T. A., & Dani, J. A. (2009) · Biochemical Pharmacology · doi:10.1016/j.bcp.2009.05.014 · Cited by 61 · cited 1× · see citing works
“Furthermore, electrophysiological studies have shown that VTA dopamine neurons are more sensitive to nicotine-induced synaptic plasticity in adolescents than adults (Placzek et al., 2009).”
BackgroundJenssen, B. P., & Boykan, R. (2019) · Children · doi:10.3390/children6020030 · Cited by 61 · see citing works
Shram, M. J., Siu, E. C. K., Li, Z., Tyndale, R. F., & Lê, A. D. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1115-x · Cited by 60 · cited 3× · see citing works
“Affective signs of withdrawal, as measured by anxiety-like behaviors on the elevated plus maze and open field, increased brain reward threshold, conditioned place avoidance, and depressive-like behaviors in the forced swim test, are also generally found to be lower in adolescent rats and mice of both sexes than adults…”
BackgroundTobacco use across the formative years: a road map to developmental vulnerabilities
Jamner, L., Whalen, C., Loughlin, S., Mermelstein, R., Audrain-McGovern, J., Krishnan-Sarin, S., Worden, J., & Leslie, F. (2003) · Nicotine & Tobacco Research · doi:10.1080/14622200310001625573 · Cited by 60 · cited 1× · see citing works
“There is a strong association between teen use of tobacco products and anxiety and depression (Patton et al., 1998; Jamner et al., 2003; McKenzie et al., 2010; Leventhal et al., 2016; Cho et al., 2018).”
BackgroundSelf-citationKelley, B. M., & Rowan, J. D. (2004) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2004.04.002 · Cited by 59 · cited 2× · see citing works
“Nicotine treatment during early adolescence also increases subsequent cocaine-induced locomotor sensitization (Kelley & Rowan, 2004; McQuown et al., 2009; Alajaji et al., 2016; Reed and Izenwasser, 2017).”
BackgroundCraig, E. L., Zhao, B., Cui, J. Z., Novalen, M., Miksys, S., & Tyndale, R. F. (2014) · Drug Metabolism and Disposition · doi:10.1124/dmd.114.058719 · Cited by 59 · see citing works
Kinnunen, J. M., Ollila, H., Minkkinen, J., Lindfors, P. L., Timberlake, D. S., & Rimpelä, A. H. (2019) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2019.04.019 · Cited by 55 · cited 1× · see citing works
“These findings are also consistent with clinical data which show that teen e-cigarette use is associated with greater risk for subsequent initiation and continuation of cigarette smoking (Soneji et al, 2017; Kinnunen et al., 2019).”
ResultAge-and sex-related differences in alcohol and nicotine effects in C57BL/6J mice
Lopez, M., Simpson, D., White, N., & Randall, C. (2003) · Addiction Biology · doi:10.1080/13556210310001648176 · Cited by 51 · cited 1× · see citing works
“Whereas nicotine inhibits locomotor activity in late adolescence and adulthood, it either has no effect (Lopez et al., 2003; Belluzzi et al., 2004; Miller et al., 2019) or stimulates motor activity in early adolescence (Adriani et al.”
BackgroundWhere Is the Pleasure in That? Low Hedonic Capacity Predicts Smoking Onset and Escalation
Audrain-McGovern, J. E., Rodriguez, D., Leventhal, A. M., Cuevas, J., Rodgers, K., & Sass, J. (2012) · Nicotine & Tobacco Research · doi:10.1093/ntr/nts017 · Cited by 51 · cited 1× · see citing works
“Other predictors of teen and young adult smoking include anhedonia, aggression, low hedonic capacity and lower distress tolerance (Roberts et al., 2010; Audrain-McGovern et al., 2012; Trujillo et al., 2016; Stone et al., 2017; Trucco et al., 2018).”
BackgroundVoos, N., Smith, D., Kaiser, L., Mahoney, M. C., Bradizza, C. M., Kozlowski, L. T., Benowitz, N. L., O’Connor, R. J., & Goniewicz, M. L. (2020) · Psychopharmacology · doi:10.1007/s00213-019-05386-x · Cited by 51 · cited 1× · see citing works
“Flavorants can lead to different patterns of nicotine delivery and a decreased perception of risk (Voos et al., 2019; Jensenn and Boykan, 2019; Boccio et al., 2020).”
BackgroundThomas, A. M., Ostroumov, A., Kimmey, B. A., Taormina, M. B., Holden, W. M., Kim, K., Brown-Mangum, T., & Dani, J. A. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.03.030 · Cited by 50 · cited 1× · see citing works
“Passive exposure to nicotine during adolescence, but not adulthood, also leads to a subsequent increase in ethanol intake in adults (Thomas et al., 2018).”
BackgroundThe natural course of nicotine dependence symptoms among adolescent smokers
Zhan, W., Dierker, L. C., Rose, J. S., Selya, A., & Mermelstein, R. J. (2012) · Nicotine & Tobacco Research · doi:10.1093/ntr/nts031 · Cited by 49 · see citing works
Locomotor and stress responses to nicotine differ in adolescent and adult rats
Cao, J., Belluzzi, J. D., Loughlin, S. E., Dao, J. M., Chen, Y., & Leslie, F. M. (2010) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2010.04.010 · Cited by 47 · cited 3× · see citing works
“It is possible that the age-dependent increase in the anxiogenic effect of nicotine reflects an activation of the stress response in adults, which is greater in females than males (Cao et al., 2010).”
BackgroundSelf-citationNatividad, L. A., Torres, O. V., Friedman, T. C., & O’Dell, L. E. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.10.003 · Cited by 45 · see citing works
Threshold of adulthood for the onset of nicotine self-administration in male and female rats
Levin, E. D., Slade, S. K., Wells, C., Cauley, M. C., Petro, A. E., Vendittelli, A., Johnson, M. L., Williams, P., Horton, K., & Rezvani, A. H. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.08.005 · Cited by 45 · see citing works
Ahsan, H. M., I. de la Peña, J. B., Botanas, C. J., Kim, H. J., Yu, G. Y., & Cheong, J. H. (2014) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2014.056 · Cited by 42 · cited 2× · see citing works
“Although nicotine is more rapidly metabolized in rodents during pre-adolescence (P23–25) than in adults, leading to lower blood levels, no pharmacokinetic differences have been seen during the adolescent period starting at P28 (Portugal et al., 2012; Ahsan et al., 2014; Craig et al., 2014; Arany et al., 2017).”
BackgroundBritton, A. F., Vann, R. E., & Robinson, S. E. (2007) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.106.112730 · Cited by 42 · cited 1× · see citing works
“In vitro rubidium efflux assays have shown α4β2* nAChRs to have higher functional activity in striatum and other brain regions in adolescents than adults (Britton et al., 2007; Kota et al., 2007).”
BackgroundSex differences in conditioned nicotine reward are age-specific
Lenoir, M., Starosciak, A. K., Ledon, J., Booth, C., Zakharova, E., Wade, D., Vignoli, B., & Izenwasser, S. (2015) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2015.02.019 · Cited by 40 · cited 2× · see citing works
“Whereas adults of both sexes experience aversive effects of high doses of nicotine, adolescents tolerate the drug well (Adriani et al., 2002; Shram et al., 2006; Torres et al., 2008, 2009; Lenoir et al., 2015).”
BackgroundMcQuown, S. C., Dao, J. M., Belluzzi, J. D., & Leslie, F. M. (2009) · Psychopharmacology · doi:10.1007/s00213-009-1642-0 · Cited by 39 · cited 1× · see citing works
“Nicotine treatment during early adolescence also increases subsequent cocaine-induced locomotor sensitization (Kelley & Rowan, 2004; McQuown et al., 2009; Alajaji et al., 2016; Reed and Izenwasser, 2017).”
BackgroundSelf-citationEarly adolescent nicotine exposure affects later-life cocaine reward in mice
Alajaji, M., Lazenka, M. F., Kota, D., Wise, L. E., Younis, R. M., Carroll, F. I., Levine, A., Selley, D. E., Sim-Selley, L. J., & Damaj, M. I. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.01.032 · Cited by 39 · cited 3× · see citing works
“Nicotine treatment during early adolescence also increases subsequent cocaine-induced locomotor sensitization (Kelley & Rowan, 2004; McQuown et al., 2009; Alajaji et al., 2016; Reed and Izenwasser, 2017).”
BackgroundHolliday, E. D., Nucero, P., Kutlu, M. G., Oliver, C., Connelly, K. L., Gould, T. J., & Unterwald, E. M. (2016) · European Journal of Neuroscience · doi:10.1111/ejn.13398 · Cited by 38 · see citing works
Xue, S., Behnood-Rod, A., Wilson, R., Wilks, I., Tan, S., & Bruijnzeel, A. W. (2020) · Nicotine & Tobacco Research · doi:10.1093/ntr/nty249 · Cited by 38 · cited 2× · see citing works
“…uthor M anuscript measured by reduction in brain reward thresholds, there was no sex difference in the rewarding effects of nicotine in adults, whereas adolescent females (P40–59) were significantly more sensitive to the rewarding effect of nicotine than their male counterparts (Xue et al., 2020).”
BackgroundAdolescent Rats Self-Administer Less Nicotine Than Adults at Low Doses
Schassburger, R. L., Pitzer, E. M., Smith, T. T., Rupprecht, L. E., Thiels, E., Donny, E. C., & Sved, A. F. (2016) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntw006 · Cited by 36 · see citing works
Cho, J., Goldenson, N. I., Stone, M. D., McConnell, R., Barrington‐Trimis, J. L., Chou, C., Sussman, S. Y., Riggs, N. R., & Leventhal, A. M. (2017) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntx270 · Cited by 36 · cited 1× · see citing works
“There is a strong association between teen use of tobacco products and anxiety and depression (Patton et al., 1998; Jamner et al., 2003; McKenzie et al., 2010; Leventhal et al., 2016; Cho et al., 2018).”
BackgroundCorongiu, S., Dessì, C., & Cadoni, C. (2020) · Addiction Biology · doi:10.1111/adb.12721 · Cited by 36 · cited 2× · see citing works
“In vivo microdialysis has confirmed that nicotine induces greater release of dopamine in the nucleus accumbens of adolescents than adults (Corongiu et al., 2020).”
BackgroundSoule, E. K., Lee, J. G. L., Egan, K. L., Bode, K. M., Desrosiers, A. C., Guy, M. C., Breland, A., & Fagan, P. (2020) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2020.107886 · Cited by 36 · see citing works
Dickson, P. E., Miller, M. M., Rogers, T. D., Blaha, C. D., & Mittleman, G. (2012) · Addiction Biology · doi:10.1111/j.1369-1600.2012.00496.x · Cited by 35 · cited 1× · see citing works
“Other studies, using the self-administration procedure, have shown that nicotine pretreatment of adolescents, but not adults, increases the subsequent reinforcing effects of cocaine (McQuown et al., 2007; Dao et al., 2011; Reed & Izenwasser, 2017; Dickson et al., 2014; Linker et al., 2020), but see (Levin et al.”
ResultSelf-administration of nicotine and cigarette smoke extract in adolescent and adult rats
Gellner, C. A., Belluzzi, J. D., & Leslie, F. M. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.06.026 · Cited by 35 · cited 3× · see citing works
“Some of the increased drug intake in adolescents in intravenous self-administration tests may reflect elevated motor activity and non-specific increases in responding (Gellner et al., 2016).”
BackgroundSelf-citationPomfrey, R. L., Bostwick, T. A., Wetzell, B., & Riley, A. L. (2015) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2015.08.004 · Cited by 34 · see citing works
Nicotine increases alcohol intake in adolescent male rats
Lárraga, A., Belluzzi, J. D., & Leslie, F. M. (2017) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2017.00025 · Cited by 33 · cited 4× · see citing works
“When adult males were pretreated with the kappa opioid receptor antagonist, norbinaltorphimine, to block this they self-administered the drug combination at the same high rate as adolescents (Lárraga et al., 2017).”
BackgroundMethodInfluentialSelf-citationPushkin, A. N., Dukes, A. J., Lallai, V., Torres-Mendoza, A., Fowler, J. P., Chen, E., & Fowler, C. D. (2019) · PLoS ONE · doi:10.1371/journal.pone.0211346 · Cited by 31 · cited 2× · see citing works
“…argued that these preclinical studies, which use fairly high doses of nicotine, do not adequately model the use of tobacco products in teenagers (Pushkin et al., 2019), it should be noted that Juul and other vape pod systems result in adolescent exposure to high doses of nicotine and subsequent…”
BackgroundElectronic cigarettes: smoke-free laws, sale restrictions, and the public health
Paradise, J. (2014) · American Journal of Public Health · doi:10.2105/ajph.2014.301890 · Cited by 30 · cited 1× · see citing works
“To date there has been insufficient regulation of these potentially dangerous tobacco products and, as a result, they have been readily available to minors in some states (Paradise, 2014).”
BackgroundBiological underpinnings of an internalizing pathway to alcohol, cigarette, and marijuana use.
Trucco, E. M., Villafuerte, S. M., Hussong, A. M., Burmeister, M., & Zucker, R. A. (2017) · Journal of Abnormal Psychology · doi:10.1037/abn0000310 · Cited by 30 · cited 1× · see citing works
“Other predictors of teen and young adult smoking include anhedonia, aggression, low hedonic capacity and lower distress tolerance (Roberts et al., 2010; Audrain-McGovern et al., 2012; Trujillo et al., 2016; Stone et al., 2017; Trucco et al., 2018).”
BackgroundAdolescent nicotine exposure disrupts context conditioning in adulthood in rats
Spaeth, A. M., Barnet, R. C., Hunt, P. S., & Burk, J. A. (2010) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2010.07.011 · Cited by 29 · cited 2× · see citing works
“Similar performance decrements were observed in another contextual conditioning task following adolescent nicotine treatment (Spaeth et al., 2010).”
BackgroundResultHughes, J. R., & Callas, P. W. (2019) · Addictive Behaviors · doi:10.1016/j.addbeh.2018.07.002 · Cited by 29 · see citing works
de la Peña, J. B., Ahsan, H. M., Tampus, R., Botanas, C. J., dela Peña, I. J., Kim, H. J., Sohn, A., dela Peña, I., Shin, C. Y., Ryu, J. H., et al. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.06.014 · Cited by 28 · cited 1× · see citing works
“Two studies in which an inhalation method for tobacco smoke or nicotine was used did note substantial physical withdrawal in adolescents, although adults were not included for comparison (de la Pena, 2015; Kallupi et al., 2019).”
ResultThe association between problematic alcohol use, risk perceptions, and e-cigarette use
Roys, M. R., Peltier, M. R., Stewart, S. A., Waters, A. F., Waldo, K. M., & Copeland, A. L. (2019) · The American Journal of Drug and Alcohol Abuse · doi:10.1080/00952990.2019.1654486 · Cited by 28 · cited 1× · see citing works
“These preclinical findings suggest that teen nicotine vaping may result in similar long-term deleterious effects, and are consistent with recent observations of linkages between vaping and substance use, mental health problems and impulsivity (Grant et al., 2019; Roys et al., 2019).”
ResultEhlinger, D. G., Bergstrom, H. C., Burke, J. C., Fernandez, G. M., McDonald, C. G., & Smith, R. F. (2014) · Brain Structure and Function · doi:10.1007/s00429-014-0897-3 · Cited by 27 · see citing works
Hamilton, K. R., Perry, M. E., Berger, S. S., & Grunberg, N. E. (2010) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntq179 · Cited by 27 · cited 1× · see citing works
“Strain differences have also been noted in adolescent physical withdrawal signs (Hamilton et al., 2010); whereas Sprague Dawley rats of both sexes were found to show significant withdrawal signs for two days after nicotine removal, Long Evans rats exhibit shortened (males) or non-existent (females) withdrawal.”
BackgroundPark, M. K., Belluzzi, J. D., Han, S.-H., Cao, J., & Leslie, F. M. (2007) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2006.10.002 · Cited by 26 · cited 1× · see citing works
“This finding is consistent with an earlier study in which selfadministration of nicotine with the tobacco constituent, acetaldehyde, was compared across sex and age (Park et al., 2007).”
ResultSelf-citationKallupi, M., de Guglielmo, G., Larrosa, E., & George, O. (2019) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2019.08.299 · Cited by 25 · cited 2× · see citing works
“Adolescent nicotine treatment increases subsequent nicotine reward and decreases aversion in adults (Adriani et al., 2003; Torres et al., 2008; Kallupi et al., 2019).”
BackgroundResultNatividad, L. A., Buczynski, M. W., Parsons, L. H., Torres, O. V., & O’Dell, L. E. (2012) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2012.07926.x · Cited by 24 · see citing works
Nicotine produces long-term increases in cocaine reinforcement in adolescent but not adult rats
Reed, S. C., & Izenwasser, S. (2017) · Brain Research · doi:10.1016/j.brainres.2016.07.044 · Cited by 23 · cited 1× · see citing works
“Nicotine treatment during early adolescence also increases subsequent cocaine-induced locomotor sensitization (Kelley & Rowan, 2004; McQuown et al., 2009; Alajaji et al., 2016; Reed and Izenwasser, 2017).”
BackgroundSlotkin, T. A., & Seidler, F. J. (2009) · Developmental Neuroscience · doi:10.1159/000207494 · Cited by 22 · see citing works
Trujillo, Á., Obando, D., & Trujillo, C. (2016) · Addictive Behaviours · doi:10.1016/j.addbeh.2016.06.020 · Cited by 22 · cited 1× · see citing works
“Other predictors of teen and young adult smoking include anhedonia, aggression, low hedonic capacity and lower distress tolerance (Roberts et al., 2010; Audrain-McGovern et al., 2012; Trujillo et al., 2016; Stone et al., 2017; Trucco et al., 2018).”
BackgroundPipkin, J. A., Kaplan, G. J., Plant, C. P., Eaton, S. E., Gil, S. M., Zavala, A. R., & Crawford, C. A. (2014) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2014.06.029 · Cited by 21 · cited 3× · see citing works
“A similar increase in methamphetamine and ethanol intake following adolescent nicotine treatment has also been seen (Dao et al., 2011; Pipkin et al., 2014).”
BackgroundThe Hippocampus in Clinical Neuroscience
Szabo, K. 1. (2014) · Monographs in clinical neuroscience/Frontiers of neurology and neuroscience/Monographs in neural sciences · doi:10.1159/isbn.978-3-318-02568-2 · Cited by 20 · see citing works
Anker, J. J., & Carroll, M. E. (2011) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2011.02.016 · Cited by 19 · see citing works
de la Peña, J. B., Ahsan, H. M., Botanas, C. J., dela Peña, I. J., Woo, T., Kim, H. J., & Cheong, J. H. (2016) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2016.09.007 · Cited by 19 · see citing works
Age-dependent alterations in reward-seeking behavior after brief nicotine exposure
Mojica, C. Y., Belluzzi, J. D., & Leslie, F. M. (2014) · Psychopharmacology · doi:10.1007/s00213-013-3266-7 · Cited by 17 · cited 3× · see citing works
“Whereas initial self-administration is enhanced by adolescent nicotine treatment, there is not a similar increase in drug-primed reinstatement (Mojica et al., 2014; Pipkin et al., 2014), although one study of preadolescent animals found an increase in cue-induced drug seeking behavior in a high sucrose preferring rat…”
BackgroundSelf-citationSchochet, T. L., Bremer, Q. Z., Brownfield, M. S., Kelley, A. E., & Landry, C. F. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06483.x · Cited by 14 · see citing works
Cross, S. J., Reynaga, D. D., Cano, M., Belluzzi, J. D., Zaveri, N. T., & Leslie, F. M. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.107846 · Cited by 14 · cited 1× · see citing works
“Alternatively, tobacco constituents, which have been shown to enhance reinstatement of nicotine seeking behavior (Costello et al., 2014; Cross et al., 2020), may increase withdrawal signs.”
BackgroundSelf-citationBoccio, C. M., Jackson, D. B., & Leal, W. E. (2020) · Addictive Behaviors · doi:10.1016/j.addbeh.2019.106186 · Cited by 13 · cited 1× · see citing works
“Flavorants can lead to different patterns of nicotine delivery and a decreased perception of risk (Voos et al., 2019; Jensenn and Boykan, 2019; Boccio et al., 2020).”
BackgroundAge-dependent effects of initial exposure to nicotine on serotonin neurons
Bang, S. J., & Commons, K. G. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.01.032 · Cited by 12 · see citing works
Kota, D., Alajaji, M., Bagdas, D., Selley, D. E., Sim-Selley, L. J., & Damaj, M. I. (2018) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2018.08.006 · Cited by 12 · cited 1× · see citing works
“Animals treated with nicotine during early adolescence, but not late adolescence or adulthood, have been found to have enhanced rewarding effects of cocaine, methamphetamine and morphine, as measured by conditioned place preference later in adulthood (McMillen et al., 2005; Alajaji et al., 2016; Kota et al., 2018; Cad…”
BackgroundHolliday, E. D., & Gould, T. J. (2016) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntw176 · Cited by 10 · cited 1× · see citing works
“Contextual fear learning is a hippocampal-dependent task in which performance is impacted by adolescent nicotine treatment (Holliday and Gould, 2016; Holliday et al., 2016).”
BackgroundCadoni, C., De Felice, M., Corongiu, S., Dessì, C., Espa, E., Melis, M., & Fenu, S. (2020) · Addiction Biology · doi:10.1111/adb.12803 · Cited by 10 · cited 3× · see citing works
“Animals treated with nicotine during early adolescence, but not late adolescence or adulthood, have been found to have enhanced rewarding effects of cocaine, methamphetamine and morphine, as measured by conditioned place preference later in adulthood (McMillen et al., 2005; Alajaji et al., 2016; Kota et al., 2018; Cad…”
BackgroundHughes, J. R., Peters, E. N., Callas, P. W., Peasley-Miklus, C., Oga, E., Etter, J.-F., & Morley, N. (2020) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntz169 · Cited by 10 · cited 1× · see citing works
“There is limited research on withdrawal from e-cigarettes, but recent analysis of the US Population Assessment of Tobacco and Health Survey and a clinical trial by the same investgators indicated that withdrawal symptoms were mild in never smokers (Hughes & Callas, 2019; Hughes et al., 2020), whereas another study of…”
Miller, C. N., Caruso, M. J., & Kamens, H. M. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2018.10.014 · Cited by 8 · cited 1× · see citing works
“Whereas nicotine inhibits locomotor activity in late adolescence and adulthood, it either has no effect (Lopez et al., 2003; Belluzzi et al., 2004; Miller et al., 2019) or stimulates motor activity in early adolescence (Adriani et al.”
BackgroundKutlu, M. G., Braak, D. C., Tumolo, J. M., & Gould, T. J. (2016) · Brain Research · doi:10.1016/j.brainres.2016.04.023 · Cited by 7 · see citing works
Age-dependent sensitivity of the mouse kidney to chronic nicotine exposure
Arany, I., Hall, S., & Dixit, M. P. (2017) · Pediatric Research · doi:10.1038/pr.2017.153 · Cited by 7 · cited 1× · see citing works
“Although nicotine is more rapidly metabolized in rodents during pre-adolescence (P23–25) than in adults, leading to lower blood levels, no pharmacokinetic differences have been seen during the adolescent period starting at P28 (Portugal et al., 2012; Ahsan et al., 2014; Craig et al., 2014; Arany et al., 2017).”
BackgroundDifferential expression of nicotine withdrawal as a function of developmental age in the rat
Keeley, R. J., Mayer, T. E., Hsu, L., Lu, H., Yang, Y., & Stein, E. A. (2019) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2019.172802 · Cited by 3 · cited 1× · see citing works
“In most studies, male adolescents have been found to exhibit less prominent somatic withdrawal symptoms than adults (O’Dell et al., 2006; Kota et al., 2007; Shram et al., 2008; Keeley et al., 2019), although female adolescent mice have been reported to show increased physical withdrawal signs as compared to adults (Ko…”
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Balancing Consideration of the Risks and Benefits of E-Cigarettes
Balfour, D. J. K., Benowitz, N. L., Colby, S. M., Hatsukami, D. K., Lando, H. A., Leischow, S. J., Lerman, C. E., Mermelstein, R. J., NIAURA, R. S., Perkins, K. A., et al. (2021) · American Journal of Public Health · doi:10.2105/ajph.2021.306416 · Cited by 326 · see citing works
“These studies lead some researchers to suspect that adolescent nicotine use in any form may lead to long-term structural and functional brain changes with associated negative implications for cognition or impulse control.(138) However, given species differences and questions about the relevance of experimental animal…”
BackgroundConsequences of adolescent drug use
Steinfeld, M. R., & Torregrossa, M. M. (2023) · Translational Psychiatry · doi:10.1038/s41398-023-02590-4 · Cited by 237 · see citing works
“For example, while nicotine inhibits microglia activation in adults, the opposite effect has been found in adolescents [186].”
BackgroundNicotine on the developing brain.
Castro, E. M., Lotfipour, S., & Leslie, F. M. (2023) · Pharmacological research · doi:10.1016/j.phrs.2023.106716 · Cited by 140 · see citing works
Self-citationEnvironmental Toxicant Exposure and Depressive Symptoms
Guo, J., Garshick, E., Si, F., Tang, Z., Lian, X., Wang, Y. Q., Li, J., & Koutrakis, P. (2024) · JAMA Network Open · doi:10.1001/jamanetworkopen.2024.20259 · Cited by 111 · see citing works
Nicotine’s effect on cognition, a friend or foe?
Wang, Q., Du, W., Wang, H., Geng, P., Sun, Y., Zhang, J., Wang, W., & Jin, X. (2023) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2023.110723 · Cited by 66 · see citing works
Colyer-Patel, K., Kuhns, L., Weidema, A., Lesscher, H., & Cousijn, J. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105038 · Cited by 54 · see citing works
“, 2015; Gould, 2010), only two reviews have addressed how effects may differ between adolescence and adulthood (Leslie, 2020; Yuan et al., 2015).”
BackgroundResultInfluentialVaping and harm in young people: umbrella review
Golder, S., Hartwell, G., Barnett, L. M., Nash, S., Petticrew, M. P., & Glover, R. E. (2025) · Tobacco Control · doi:10.1136/tc-2024-059219 · Cited by 51 · see citing works
“Another striking gap in the evidence we collected, given the considerable interest in the role of nicotine on neurodevelopment, 103 104 is the potential influence of e-cigarettes on adolescent brain development.”
E-cigarettes may serve as a gateway to conventional cigarettes and other addictive drugs
Chen, G. L., Rahman, S., & Lutfy, K. (2023) · Advances in Drug and Alcohol Research · doi:10.3389/adar.2023.11345 · Cited by 47 · see citing works
Unique effects of nicotine across the lifespan
Ren, M., Lotfipour, S., & Leslie, F. (2022) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2022.173343 · Cited by 40 · see citing works
“…et al., 2002 Dorn, 1959 (continued on next page) M. Ren et al. Pharmacology, Biochemistry and Behavior 214 (2022) 173343 rewarding effects of drugs of abuse (Leslie, 2020; Ren and Lotfipour, 2019; Yuan et al., 2015), decreased attention and other learning/ memory deficits (Counotte et al.,…”
BackgroundSelf-citationSex Differences in E-Cigarette Use and Related Health Effects
Alam, F., & Silveyra, P. (2023) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph20227079 · Cited by 38 · see citing works
“In terms of the central nervous system, a few studies have been conducted assessing sex differences, with special attention being paid to the effects of nicotine on the male and female brain [85].”
BackgroundShaikh, S. B., Tung, W. C., Lucas, J., Yogeswaran, S., Li, D., & Rahman, I. (2022) · Toxics · doi:10.3390/toxics10110660 · Cited by 39 · see citing works
“tional dysregulation and decreased cognitive functioning [3].”
BackgroundBall, J., Fleming, T. M., Drayton, B., et al. (2021) · Australian and New Zealand Journal of Public Health · doi:10.1111/1753-6405.13169 · Cited by 31 · see citing works
Xie, C. Z., Xie, Z., & Li, D. (2020) · Tobacco Induced Diseases · doi:10.18332/tid/130925 · Cited by 30 · see citing works
Saliva and Lung Microbiome Associations with Electronic Cigarette Use and Smoking
Ying, K. L., Brasky, T. M., Freudenheim, J. L., McElroy, J., Nickerson, Q. A., Song, M., Weng, D. Y., Wewers, M. D., Whiteman, N. B., Mathé, E. A., et al. (2022) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-21-0601 · Cited by 28 · see citing works
Nicotine and Cardiovascular Health: When Poison is Addictive – a WHF Policy Brief
Dorotheo, E. U., Arora, M., Banerjee, A., Bianco, E., Cheah, N. P., Dalmau, R., Eissenberg, T., Hasegawa, K., Naidoo, P., Nazir, N. T., et al. (2024) · Global Heart · doi:10.5334/gh.1292 · Cited by 28 · see citing works
Association between vmPFC gray matter volume and smoking initiation in adolescents
Xiang, S., Jia, T., Xie, C., Cheng, W., Chaarani, B., Banaschewski, T., Barker, G. J., Bokde, A. L. W., Büchel, C., Desrivières, S., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-40079-2 · Cited by 30 · see citing works
Reynolds, L. M., Faure, P., & Barik, J. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03110-0 · Cited by 26 · see citing works
“Nicotine in adolescence has been shown to increase later sensitivity to the rewarding effects of nicotine, while decreasing its aversive effects; these studies have been thoroughly reviewed elsewhere, see: [90, 92]).”
Factors that influence decision-making among youth who vape and youth who don’t vape
Struik, L. C., Christianson, K., Khan, S., et al. (2023) · Addictive Behaviors Reports · doi:10.1016/j.abrep.2023.100509 · Cited by 25 · see citing works
“Increased impulsivity, mood swings and depression are seen among youth who vape (Leslie, 2020).”
BackgroundPrice elasticity of demand for cigarettes among youths in high-income countries: a systematic review
Kjeld, S. G., Jørgensen, M. B., Aundal, M., & Bast, L. S. (2021) · Scandinavian Journal of Public Health · doi:10.1177/14034948211047778 · Cited by 24 · see citing works
Merianos, A. L., Mahabee‐Gittens, E. M., Hill, M. J., Olaniyan, A. C., Smith, M. L., & Choi, K. (2023) · Preventive Medicine · doi:10.1016/j.ypmed.2023.107712 · Cited by 21 · see citing works
Joannès, C., Castagné, R., & Kelly‐Irving, M. (2022) · Preventive Medicine · doi:10.1016/j.ypmed.2022.106995 · Cited by 21 · see citing works
Health outcomes of electronic cigarettes
Li, X., Yuan, L., & Wang, F. (2024) · Chinese Medical Journal · doi:10.1097/cm9.0000000000003098 · Cited by 20 · see citing works
“[75] Among the e-cigarette users, only the e-cigarette-with-nicotine group exhibited acute increases in blood pressure and heart rate, indicating that these sympathetic effects are attributable to nicotine instead of other compounds in the aerosols.”
BackgroundGaiha, S. M., Halpern‐Felsher, B. L., Feld, A. L., et al. (2021) · Preventive Medicine Reports · doi:10.1016/j.pmedr.2021.101457 · Cited by 19 · see citing works
“Further, nicotine interferes with and changes the developing brain, resulting in greater likelihood of becoming nicotine dependent (Yuan et al., 2015; Leslie, 2020).”
BackgroundChemosensory Contributions of E-Cigarette Additives on Nicotine Use
Johnson, N. L., Patten, T., Ma, M., Biasi, M. D., & Wesson, D. W. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.893587 · Cited by 19 · see citing works
“Nicotine use, especially during adolescence, results in short- and long-term detriments to brain development (Slotkin, 2004; Yuan et al., 2015; Leslie, 2020), reward processing (Mansvelder et al., 2002; Hilario et al., 2012; Ren and Lotfipour, 2019), and overall health (Picciotto et al., 2002; Lee…”
BackgroundE-Cigarettes Reexamined: Product Toxicity
Pipe, A., & Mir, H. R. (2022) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2022.08.001 · Cited by 20 · see citing works
Jones, E. J., Endrighi, R., Weinstein, D. J., Jankowski, A., Quintiliani, L., & Borrelli, B. (2023) · Addictive Behaviours · doi:10.1016/j.addbeh.2023.107835 · Cited by 18 · see citing works
Sim, Y. S., Yoo, S., Lee, K., Rhee, C. K., & Kim, Y. K. (2021) · Scientific Reports · doi:10.1038/s41598-021-97387-0 · Cited by 18 · see citing works
Wade, N. E., Courtney, K. E., Doran, N., Baca, R. E., Aguinaldo, L. D., Thompson, C., Finegan, J. L., & Jacobus, J. (2022) · Brain Sciences · doi:10.3390/brainsci12070889 · Cited by 17 · see citing works
“Cognitive differences in adolescent and young adult NTP users have been noted previously [13,14,53], though not always [53,54].”
BackgroundBaiden, P., Spoor, S. P., Nicholas, J. K., Brown, F. A., LaBrenz, C. A., & Spadola, C. (2022) · Sleep Medicine · doi:10.1016/j.sleep.2022.10.005 · Cited by 18 · see citing works
Frie, J. A., McCunn, P., Eed, A., Hassan, A., Luciani, K. R., Chen, C., Tyndale, R. F., & Khokhar, J. Y. (2023) · Neuropsychopharmacology · doi:10.1038/s41386-023-01773-3 · Cited by 16 · see citing works
“Adult females had signi fi cantly greater nicotine and cotinine plasma levels at the 10-min timepoint compared to adolescent females.”
Alzoubi, K. H., Batran, R. M., Al‐Sawalha, N. A., Khabour, O. F., Karaoghlanian, N. V., Shihadeh, A., & Eissenberg, T. (2021) · Inhalation Toxicology · doi:10.1080/08958378.2021.1954732 · Cited by 17 · see citing works
My friends made me do it: Peer influences and different types of vaping in adolescence
Skinner, A. T., Golonka, M. M., Godwin, J. W., Kwiatek, S. M., Sweitzer, M. M., & Hoyle, R. H. (2024) · Addictive Behaviors · doi:10.1016/j.addbeh.2024.108128 · Cited by 16 · see citing works
Curiosity, use, and perceptions of “tobacco-free nicotine” E-cigarettes among U.S. young adults
Camenga, D. R., Krishnan‐Sarin, S., Davis, D. R., Bold, K. W., Kong, G., & Morean, M. E. (2022) · Preventive Medicine · doi:10.1016/j.ypmed.2022.107296 · Cited by 16 · see citing works
Adjei, A., Chen, B.-J., Mantey, D. S., Wilkinson, A. V., & Harrell, M. B. (2023) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2023.111059 · Cited by 16 · see citing works
Cardenas, A., & Lotfipour, S. (2022) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntab218 · Cited by 16 · see citing works
Nicotine replacement therapy as a smoking cessation tool for adolescents: an update
Beis, I., Dimou, A., Kotoulas, S., & Pataka, A. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1525510 · Cited by 16 · see citing works
“Research suggests that nicotine exposure during adolescence can negatively impact brain regions involved in decision-making, memory, and impulse control, raising ethical and safety concerns about encouraging NRT use in this population (8).”
Elatfy, A., Vrahimis, S., Conti, A. A., & Baldacchino, A. (2024) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2024.1384408 · Cited by 15 · see citing works
“Alongside this, a neuroimaging study conducted by Conti and Baldacchino (68) reported a correlation between the age of regular smoking initiation during adolescence (16 years) and reduced Gray Matter (GM) volume in the VLPFC of chronic tobacco smokers (69, 70).”
BackgroundE-Cigarettes and the Nicotine Epidemic: Statement From the International Pediatric Association
Arora, M., Kulkarni, M. M., Ghosal, S., Sathyan, A., Gupta, M., Verma, S., Farmer, M. Y., Hadjipanayis, A., Klein, J. D., Winickoff, J. P., et al. (2025) · PEDIATRICS · doi:10.1542/peds.2025-072337 · Cited by 14 · see citing works
Chronic Obstructive Pulmonary Disease and Depression—The Vicious Mental Cycle
Corlăteanu, A., Covanţev, S., Iasabash, O., Lupu, L., Avadanii, M., & Siafakas, N. (2025) · Healthcare · doi:10.3390/healthcare13141699 · Cited by 15 · see citing works
From Tobacco Cigarettes to Electronic Cigarettes: The Two Sides of a Nicotine Coin
Nia, A. B. (2021) · Frontiers in Oral Health · doi:10.3389/froh.2021.790634 · Cited by 12 · see citing works
Conti, A. A., & Baldacchino, A. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.939707 · Cited by 12 · see citing works
Detection of vaping, cannabis use, and hazardous prescription opioid use among adolescents
Dash, G. F., Holt, L. J., Kenyon, E. A., Carter, E. K., Ho, D., Hudson, K. A., & Ewing, S. W. F. (2022) · The Lancet Child & Adolescent Health · doi:10.1016/s2352-4642(22)00212-7 · Cited by 12 · see citing works
Youths' Perceptions of Nicotine Harm and Associations With Product Use.
O'Brien, E. K., Roditis, M. L., Persoskie, A., & Margolis, K. A. (2023) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntad028 · Cited by 10 · see citing works
Happer, J. P., Courtney, K. E., Baca, R. E., Andrade, G., Thompson, C., Shen, Q., Liu, T. T., & Jacobus, J. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1436951 · Cited by 11 · see citing works
“…et al., 2019), and animal models suggest that low, intermittent doses of nicotine during adolescence can have a lasting impact on brain health and functioning that continues later into adulthood (Trauth et al., 2000; Abreu-Villaça et al., 2003; Oliveira-da-Silva et al., 2009; Leslie, 2020).”
BackgroundKids No Longer Smoke Cigarettes. Why Aren’t We Celebrating?
Warner, K. E. (2024) · American Journal of Public Health · doi:10.2105/ajph.2024.307841 · Cited by 12 · see citing works
Use of Tobacco and Nicotine Products among Young People in Denmark—Status in Single and Dual Use
Bast, L. S., Klitgaard, M. B., Kjeld, S. G., Jarlstrup, N. S., & Christensen, A. I. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19095623 · Cited by 12 · see citing works
“Moreover, nicotine negatively impacts the development of the adolescent brain [12,13].”
BackgroundElectronic Cigarettes: Are They Smoking Cessation Aids or Health Hazards?
Mir, M., Rauf, I., Goksoy, S., Khedr, A., Jama, A. B., Mushtaq, H. A., Jain, N. K., Khan, S. A., Surani, S., & Koritala, T. (2022) · Cureus · doi:10.7759/cureus.25330 · Cited by 11 · see citing works
“Neurological/behavioral Amplified rewarding effects of abused drugs, cognitive decline, and emotional imbalance [19], diminished dopaminergic state [20], altered structural and neurochemical brain development in adolescents [21]”
BackgroundReynolds, L. M., Gulmez, A., Fayad, S. L., Campos, R. C., Rigoni, D., Nguyen, C., Le Borgne, T., Topilko, T., Rajot, D., Franco, C., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-53327-w · Cited by 10 · see citing works
“…in the rewarding effects of nicotine in adolescent vs adult rats and mice and on how adolescent nicotine exposure can in fl uence later measures of nicotine reward 7,8 , but less is known about how nicotine impacts the adolescent development of neural circuitry to produce these enduring outcomes.”
BackgroundLuo, C., Wang, X., Yang, Y., Yan, Q., Sun, L., & Yang, D. (2023) · PLoS ONE · doi:10.1371/journal.pone.0285261 · Cited by 10 · see citing works
“Animal studies have shown that nicotine has effects on deficits in cognitive function and emotional dysregulation in adolescent mice [49].”
BackgroundCardenas, A. M., Bai, Y., Heydary, Y. H., Li, J., Leslie, F. M., & Lotfipour, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23063145 · Cited by 10 · see citing works
“Neuronal nAChRs are critical during the developmental period of adolescence [6] and are expressed in brain regions important for reward [7,8].”
BackgroundSelf-citationAnesthesiologists and the Other Pandemic: Tobacco Use
Warner, D. O. (2022) · Anesthesiology · doi:10.1097/aln.0000000000004346 · Cited by 9 · see citing works
Early evidence of flavored tobacco product restrictions in Massachusetts and New York State
Schillo, B., Seaman, E. L., Cuccia, A. F., et al. (2023) · Tobacco Induced Diseases · doi:10.18332/tid/172000 · Cited by 9 · see citing works
Malone, R. E., & McAfee, T. A. (2024) · Tobacco Control · doi:10.1136/tc-2024-058716 · Cited by 9 · see citing works
Brookfield, S., Chye, N. A., Carah, N., & GARTNER, C. E. (2024) · International Journal of Drug Policy · doi:10.1016/j.drugpo.2024.104513 · Cited by 10 · see citing works
Abdulhay, N., Wiener, R. C., Wen, S., Gibbs, B. B., & Bhandari, R. (2025) · PLOS mental health. · doi:10.1371/journal.pmen.0000370 · Cited by 9 · see citing works
“Adolescents who develop a dependency to nicotine, may experience disruptions in brain development, potentially affecting mood regulation, permanent damage to memory, cognitive function, and emotional control [31–34].”
Burnett, T., Battista, K., Butt, M. L., Sherifali, D., Leatherdale, S. T., & Dobbins, M. (2022) · Canadian Journal of Public Health · doi:10.17269/s41997-022-00655-3 · Cited by 9 · see citing works
“Substance use in adolescence can have serious lifelong health consequences such as lung disease, cognitive deficits, premature death and future substance use (Camchong et al., 2017; Leslie, 2020; Lubman et al., 2015; World Health Organization, 2018).”
BackgroundTobacco smoking and nicotine vaping in persons with first episode psychosis
Bennett, M. E., Medoff, D. R., Cowan, T., Fang, L., Kacmarek, C. N., Oikonomou, M. T., Calkins, M. E., Baker, K. K., Bencivengo, D. J., Boumaiz, Y., et al. (2024) · Schizophrenia Research · doi:10.1016/j.schres.2024.03.020 · Cited by 10 · see citing works
Literature Review on Nicotine’s Role in Human Health
Scherer, G., Pluym, N., & Scherer, M. (2024) · Contributions to Tobacco & Nicotine Research · doi:10.2478/cttr-2024-0001 · Cited by 8 · see citing works
Bast, L. S., Kjeld, S. G., & Klitgaard, M. B. (2022) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntac203 · Cited by 8 · see citing works
Dutra-Tavares, A. C., Manhães, A. C., Semeão, K. A., Maia, J. G., Couto, L. A., Filgueiras, C. C., Ribeiro‐Carvalho, A., & Abreu‐Villaça, Y. (2021) · PLoS ONE · doi:10.1371/journal.pone.0257986 · Cited by 9 · see citing works
Peterson, E., Pitzer, L., & Zhao, X. (2022) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntac245 · Cited by 8 · see citing works
Conti, A. A., & Baldacchino, A. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1209277 · Cited by 8 · see citing works
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“Like conventional cigarettes, most ATPs contain different levels of nicotine which is addictive and especially harmful for the young brain and brain development (Leslie, 2020; US Department of Health and Human Services, 2016).”
BackgroundBai, X., Yao, L., Duan, C., Sun, X., & Niu, G. (2022) · Behavioral Sciences · doi:10.3390/bs12120478 · Cited by 7 · see citing works
“It may cause great harm to adolescents’ health and adaptation—tobacco and alcohol use cause brain damage [2], poor academic performance [3,4], and aggressive behaviors [5] among adolescents.”
BackgroundWhite, D. A., Bush, A., Smyth, A. R., & Bhatt, J. (2023) · Breathe · doi:10.1183/20734735.0141-2023 · Cited by 7 · see citing works
“It also affects brain development which is a particular concern in children and adolescents [10].”
BackgroundInvestigation of white matter functional networks in young smokers
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“Studies have shown that adolescence is a critical period for the formation of smoking behavior and that brain functions gradually mature during this period (Leslie, 2020).”
BackgroundKjeld, S. G., Lund, L., Andersen, S., & Bast, L. S. (2022) · Frontiers in Public Health · doi:10.3389/fpubh.2022.825585 · Cited by 7 · see citing works
Li, L., Xu, G., Li, J., Wang, Y., & Bian, G. (2022) · Journal of Affective Disorders · doi:10.1016/j.jad.2022.12.099 · Cited by 7 · see citing works
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Adjei, A., Mantey, D. S., Chen, B., Wilkinson, A. V., & Harrell, M. B. (2024) · Preventive Medicine · doi:10.1016/j.ypmed.2024.107924 · Cited by 7 · see citing works
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Sais de Nicotina e Nicotina Sintética: Novos Desafios para um Velho Problema
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Unraveling the Role of CHRNA6, the Neuronal α6 Nicotinic Acetylcholine Receptor Subunit
Heydary, Y. H., Castro, E. M., Lotfipour, S., & Leslie, F. M. (2025) · Receptors · doi:10.3390/receptors4010001 · Cited by 6 · see citing works
“The adolescent brain is especially susceptible to the effects of nicotine [6], and it is essential to investigate how these receptors differ between sexes as well.”
Self-citationEffects of adolescent substance use disorders on central cholinergic function
Hauser, S. R., Rodd, Z. A., Deehan, G. A., Liang, T., Rahman, S., & Bell, R. L. (2021) · International review of neurobiology · doi:10.1016/bs.irn.2021.07.008 · Cited by 7 · see citing works
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Protecting children from harms of vaping
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“Although it is difficult in humans to confirm similar behavioral effects of teen nicotine exposure, observational studies indicate similarities between animals and humans [54].”
Early onset of e-cigarette use and subsequent use frequency among US high school students
Sun, R., & Yi, N. (2024) · Preventive Medicine Reports · doi:10.1016/j.pmedr.2024.102935 · Cited by 5 · see citing works
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“Moreover, e-cigarettes generally contain nicotine, which is highly addictive and can negatively impact brain development over the long term (11, 12), possibly leading to addictions to tobacco and other substances (13–15).”
BackgroundUnderstanding gender differences in e-cigarette use among adolescents: survey findings
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“Over the past decade, ENDS use has been increasingly prevalent in the U.S., particularly among youth and young adult populations (Birdsey et al., 2023; Cornelius et al., 2023; NASEM, 2018; Wang et al., 2018; 2020).”
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“…even the illegal sale of legal vaping products to minors is a concern, as animal studies have shown that nicotine affects the developing adolescent brain differently to the adult brain, potentially resulting in behavioural, emotional and cognitive dysregulation and greater levels of addiction 62 .”
The E-Cigarette Phenomenon: What it is, Why it is Happening, and What You Should Know About it
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“In addition, nicotine has been found to a negatively impact the development of the adolescent brain (Leslie, 2020; Yuan et al., 2015).”
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“The adverse mental effects of secondhand smoke on brain development are projected to be more severe in this age group than in adults 5 .”
BackgroundChildhood traumatic experiences and vaping among Australian adolescents: A prospective investigation
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Nationwide experiences with youth-targeted smoking and nicotine product cessation
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Vaping and Mental Health: Research Trends and Future Directions
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“Similarly, smoking (Leslie, 2020) or, now more commonly, vaping tobacco (Jenssen and Boykan, 2019) and cannabis (Jager and Ramsey, 2008; Vivian Chiu et al.”
BackgroundGonçalves, P. F. R., Nunes, L. E. D., Andrade, B. D. S., da Silva, M. O. L., Souza, I. N. D. O., Assunção‐Miranda, I., Castro, N. G., & Neves, G. A. (2023) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2023.110821 · Cited by 3 · see citing works
Impact of Vaping on Lungs: An Indian Prospect
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“There is yet little evidence that medicinal trials have an impact on oral fitness, and the majority of the research conducted so far has been small-scale and mainly cross-sectional [30,31].”
BackgroundE-cigarettes and Youth: The Known, the Unknown, and Implications for Stakeholders
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Association of Life’s Essential 8 with depression among adults: A cross-sectional study of NHANES
Bai, Y., & Guo, S. (2024) · Journal of Investigative Medicine · doi:10.1177/10815589241261286 · Cited by 6 · see citing works
“31 PA has benefits for both CVH and mental health.”
Prevalence of Blunt and Hemp Wrap Use Among Young Adults in the United States, 2022
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“Given that the adolescent brain is still developing, use of nicotine or cannabis can have a lifelong impact on the brain increasing the risks for later substance use disorders or other psychiatric conditions (Fischer et al., 2020; Leslie, 2020).”
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“…combusted tobacco use (Centers for Disease and Prevention Control, 2024; Hair et al., 2021; Tashakkori et al., 2023) and vulnerability to drug use and misuse (USDHHS, 2016) and harms brain development in adolescents (Castro et al., 2023; England et al., 2015; Leslie, 2020; Yuan et al., 2015).”
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- Authors
- Leslie, F. M.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- Leslie, Frances M.
- ORCID
- Leslie, Frances M.
- Venue
- Pharmacology, Biochemistry, and Behavior
- Publisher
- Elsevier BV
- Published
- 2020-10
- Volume
- 197
- Pages
- 173010
- ISSN
- 0091-3057 (ISSN-L)
- PMC
- PMC7484459
- OpenAlex
- W3045780954
- Cited by
- 178
- References
- 166
- Citations by year
- 2026: 32 · 2025: 33 · 2024: 35 · 2023: 29 · 2022: 35 · 2021: 13 · 2020: 1
- FWCI
- 2.49
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Pharmacology Biochemistry and Behavior (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Keywords
- adolescent nicotine exposure, adolescent brain development, nicotine vaping, electronic cigarettes, age and sex differences, drug reward, drug aversion, cognition, emotions, neurochemistry, human-animal comparison
- MeSH terms
- Vaping, Adolescent, Age Factors, Animals, Behavior, Animal, Brain, Cognition, Emotions, Female, Humans, Male, Nicotine, Receptors, Nicotinic, Reward, Substance Withdrawal Syndrome, United States, Electronic Nicotine Delivery Systems
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