The DOI matches its Crossref record; 138 of the 140 references it cites were found in a registry or an index; 78 of the 116 sources its claims cite were checked for support.
Nicotine Withdrawal
Open accessAbstract
An aversive abstinence syndrome manifests 4-24 h following cessation of chronic use of nicotine-containing products. Symptoms peak on approximately the 3rd day and taper off over the course of the following 3-4 weeks. While the severity of withdrawal symptoms is largely determined by how nicotine is consumed, certain short nucleotide polymorphisms (SNPs) have been shown to predispose individuals to consume larger amounts of nicotine more frequently--as well as to more severe symptoms of withdrawal when trying to quit. Additionally, rodent behavioral models and transgenic mouse models have revealed that specific nicotinic acetylcholine receptor (nAChR) subunits, cellular components, and neuronal circuits are critical to the expression of withdrawal symptoms. Consequently, by continuing to map neuronal circuits and nAChR subpopulations that underlie the nicotine withdrawal syndrome--and by continuing to enumerate genes that predispose carriers to nicotine addiction and exacerbated withdrawal symptoms--it will be possible to pursue personalized therapeutics that more effectively treat nicotine addiction.
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Claims the paper makes
39 Supported · 23 Partly supported · 17 No full text of the sources · 16 Own interpretation · 15 No basis given · 4 Supported so far · 4 Sources not found · 3 Not checked yet · 1 Mixed support · 1 Not supported · 1 Couldn’t confirm · accuracy not yet measured
Some cited sources support this claim and some don’t — read each source’s verdict below.
In the paper
“As replacement of β2 by β4 is sufficient to increase nAChR levels at the plasma membrane in the absence of nicotine, the proposed “chaperoning” function of nicotine might not be as effective (Srinivasan et al. 2011; Henderson et al. 2014).”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.1 nAChR Upregulation
What the sources say
- Partly supportedcites Srinivasan et al. 2011 sourceExperimental — accuracy not yet measured
The TIRF microscopy section reports 1.9-fold higher plasma-membrane receptor density with β4 than with β2, supporting the first part of the claim. The Discussion says nicotine produced only a small further increase for an enhanced-export β2 mutant designed to mimic features of β4, but the paper does not establish that nicotine chaperoning is less effective for receptors containing β4 itself. No page numbers are available in our copy. (LLM, conf=0.85)
- Disputedcites Henderson et al. 2014 sourceExperimental — accuracy not yet measured
The Results section on nicotine-induced up-regulation (page unavailable) reports a greater than threefold increase in plasma-membrane α6β4* receptors after nicotine treatment, while α6β2 receptors showed no increase at 50 nM. That is contrary to the suggested weaker nicotine effect with β4. The paper’s separate finding that β3 increases baseline membrane density does not establish the claimed effect of replacing β2 with β4. (LLM, conf=0.82)
Checked by a reasoning model — may be wrong.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Depending on the parameters used to define dependence, and the population considered, heritability contributes 50–75 % of the risk for dependence (Dokal et al. 1989; Hall et al. 2002; Lessov et al. 2004; Furberg et al. 2010; Nugent et al. 2014; also see chapters entitled Genetics of Smoking Behaviour and Pharmacogenetics of Nicotine and Associated Smoking Behaviors; volume 23).”
§ Nicotine Withdrawal > 1 Withdrawal Syndrome in Humans > 1.2 Genetic Influences
What the sources say
- Not checked — no full text of the sourcecites Dokal et al. 1989 source
- Partly supportedcites Hall et al. 2002 sourceExperimental — accuracy not yet measured
The Twin studies section says genetic influences play an important role in nicotine dependence, and the Conclusions say dependence is partially under genetic control. But the copy does not give a 50–75% heritability estimate for nicotine dependence; its numerical heritability ranges in Twin studies concern smoking initiation, a different outcome. Pages are not available in the indexed passages. (LLM, conf=0.85)
- Supportedcites Lessov et al. 2004 source
The Univariate genetic analysis reports heritability of 56% for DSM-IV nicotine dependence and 71% for the HSI definition. The Discussion also reports different estimates for smoker groups and comparisons with other twin populations, supporting the approximate 50–75% range and its dependence on definition and population. Page numbers are not provided in our copy. (LLM, conf=0.90)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Every source the paper cites for this claim was checked and supports it.
In the paper
“and there is a documented role for α6* nAChRs in withdrawal-induced CPA (Jackson et al. 2009).”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
What the sources say
- Supportedcites Jackson et al. 2009 source
The Discussion (page not provided) reports that an α6-selective antagonist blocked aversion in the conditioned place aversion model during nicotine withdrawal. The authors identify this as evidence for a role of α6* nAChRs in affective nicotine withdrawal. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“While sequence variants associated with smoking behavior lie within the regions that harbor the CHRNB3-CHRNA6 genes on chromosome 8p11 (Thorgeirsson et al. 2010)”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
What the sources say
- Supportedcites Thorgeirsson et al. 2010 source
The paper’s concluding passage states that it discovered smoking-behavior-associated variants in regions harboring CHRNB3–CHRNA6 at 8p11. Its results also report genome-wide-significant smoking-quantity associations for SNPs on chromosome 8p11. (LLM, conf=0.95)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“When the anhedonic affective state was evaluated between 8 and 100 h after nicotine withdrawal, ICSS thresholds were equally elevated in α7 WT and null littermates, indicating that a lack of α7 nAChR subunits delays, rather than abolishes, withdrawal symptoms.”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
What the sources say
- Supportedcites Stoker et al. 2012 source
The Discussion reports that α7 knockout mice lacked the early ICSS threshold elevation seen in wild-type mice, but their thresholds later rose to similar levels. This supports a delay, rather than elimination, of the anhedonic aspect of spontaneous nicotine withdrawal. (LLM, conf=0.93)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“However, the mutant mice do not exhibit anxiety-related behaviors normally associated with withdrawal from chronic nicotine exposure (Jackson et al. 2008).”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
What the sources say
- Supportedcites Jackson et al. 2008 source
The Results section reports that nicotine-dependent β2 knockout mice lacked withdrawal-induced anxiety-related behavior compared with wild-type mice. It also reports a loss of anxiety-related behavior after spontaneous withdrawal from nicotine, directly supporting the citing sentence. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The α5 null mutation does not appear to influence affective symptoms such as withdrawal-induced CPA (Jackson et al. 2008).”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
What the sources say
- Supportedcites Jackson et al. 2008 source
The Results section reports that mecamylamine-precipitated conditioned place aversion remained present in nicotine-dependent α5 knockout mice, with no genotype effect or interaction. The Discussion concludes that α5 is involved in some physical withdrawal signs but not affective withdrawal signs. (LLM, conf=0.94)
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“α2 KO mice also self-administer higher doses of nicotine than WT controls (Lotfipour et al. 2013).”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
What the sources say
- Partly supportedcites Lotfipour et al. 2013 sourceExperimental — accuracy not yet measured
The Results (Food and nicotine reinforcement; page not provided) report enhanced self-administration by α2 knockout mice during the first two days of acquisition and at the highest dose tested (0.4 mg/kg/infusion). The unqualified comparison overstates the finding: the paper reports no significant overall genotype effect during acquisition or across the four-dose response test. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In addition, β4 KO mice do not display anhedonia-like symptoms during withdrawal, as identified by unchanged intracranial self-stimulation thresholds (Stoker et al. 2012).”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
What the sources say
- Supportedcites Stoker et al. 2012 source
The Results (Spontaneous nicotine withdrawal) report no intracranial self-stimulation threshold elevations at any measured time point in nicotine-withdrawing β4 knockout mice. The summary interprets this as an apparent delay or lack of onset of the anhedonic aspects of withdrawal, consistent with the citing sentence's threshold-based claim. (LLM, conf=0.90)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Similar results were found for β4 KO mice undergoing spontaneous withdrawal from chronic nicotine administration (Stoker et al. 2012).”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
What the sources say
- Partly supportedcites Stoker et al. 2012 sourceExperimental — accuracy not yet measured
The Results (Spontaneous nicotine withdrawal; page not provided) report no increase in somatic signs in β4 knockout mice after withdrawal from 40 mg/kg/day nicotine. At 80 mg/kg/day, however, signs were attenuated compared with wildtype mice but significantly higher than in saline-treated knockout mice. The claim's unqualified absence of somatic withdrawal signs is therefore too broad. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“As β3 mRNA is detected in the substantia nigra, VTA, and medial habenula (Cui et al. 2003)”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
What the sources say
- Supportedcites Cui et al. 2003 source
The In situ hybridization section reports strong β3 mRNA expression in the substantia nigra, ventral tegmental area (VTA), and medial habenula of wild-type mice. Figure 2’s caption reports specific labeling in the same regions. (LLM, conf=0.95)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The increased pool of nAChRs arising from chronic nicotine exposure may drive symptoms associated with the nicotine withdrawal syndrome (Turner et al. 2011; Gould et al. 2012)”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.1 nAChR Upregulation
What the sources say
- Supportedcites Turner et al. 2011 source
The Introduction (page unavailable) says chronic nicotine upregulates nAChRs and discusses a possible link between that upregulation and withdrawal phenotypes. The Abstract (page unavailable) says nAChR regulation may be involved in the etiology of withdrawal symptoms, supporting the citing sentence’s tentative wording; the Discussion does not establish causation. (LLM, conf=0.86)
- Partly supportedcites Gould et al. 2012 sourceExperimental — accuracy not yet measured
The Discussion (section 4; page not supplied) suggests that nAChR upregulation may contribute to nicotine withdrawal-related learning deficits. The claim broadens this possible mechanism to withdrawal symptoms generally, whereas the paper says different symptoms involve different receptors and that its results do not demonstrate causation. (LLM, conf=0.85)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In male mice, Chrna2 deletion also produces nicotine withdrawal-induced deficits of cued FC (Lotfipour et al. 2013).”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
What the sources say
- Supportedcites Lotfipour et al. 2013 source
The Discussion (‘Role of Chrna2 in drug reinforcement and withdrawal’) explicitly reports potentiated deficits in cued fear conditioning in male Chrna2−/− mice during nicotine withdrawal. The Results (‘Fear conditioning’) add an important uncertainty: the male effect did not pass Bonferroni correction for multiple comparisons. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“α7 null mice exhibit significantly reduced withdrawal symptoms immediately after precipitation of withdrawal by mecamylamine injection (Salas et al. 2007).”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
What the sources say
- Supportedcites Salas et al. 2007 source
The Results report significantly fewer withdrawal signs in nicotine-treated α7 knockout mice than in nicotine-treated wild-type mice during the 20 minutes after a 3 mg/kg mecamylamine injection. The effect was dose-dependent: the Results found no significant genotype difference at 6 mg/kg. (LLM, conf=0.91)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“pharmacological data suggest that receptors comprising the α3 and β4 nAChR subunits influence both nicotine reward and somatic manifestations of withdrawal (Jackson et al. 2013).”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
What the sources say
- Supportedcites Jackson et al. 2013 source
The Discussion reports that pharmacological treatment with AuIB attenuated somatic withdrawal signs and concludes that α3β4* receptors mediate nicotine reward and physical withdrawal signs in mice. This supports the citing sentence’s hedged claim about both reward and somatic withdrawal. (LLM, conf=0.94)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Somatic symptoms in mice include excessive grooming, chewing, tremors, “wetdog” shakes, yawns, and teeth chattering (Paolini and De Biasi 2011).”
§ Nicotine Withdrawal > 2 Withdrawal Syndrome in Mice > 2.1 Behavioral Manifestations and Testing Paradigms
What the sources say
- Partly supportedcites Paolini and De Biasi 2011 sourceExperimental — accuracy not yet measured
Section 3.3.1, “Somatic signs of withdrawal” (page not provided), lists chewing, teeth-chattering, shakes, tremors, and yawns as somatic signs in rodents and discusses somatic withdrawal in mice. It does not mention excessive grooming or specify that the shakes are “wetdog” shakes. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Because desensitized nAChR conformations have a higher affinity for agonist, nAChRs will increasingly adopt desensitized conformations in response to chronic nicotine exposure (Quick and Lester 2002; Picciotto et al. 2008).”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.2 Desensitization of nAChRs
What the sources say
- Supportedcites Quick and Lester 2002 source
In “Molecular Aspects of Desensitization,” the paper describes desensitized states as having high affinity for agonists. In “Regulation of Desensitization,” it says continuous nicotine would drive receptors into long-lasting inactive or desensitized conformations, supporting the claimed response to chronic exposure. (LLM, conf=0.90)
- Supportedcites Picciotto et al. 2008 source
Section 1.3 (page not provided) states that desensitized nAChRs have higher affinity for ACh and other ligands and that chronic nicotine exposure likely produces long-term desensitization. Section 1.4 (page not provided) explains that continued ligand exposure stabilizes the highest-affinity, desensitized state. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In addition, a significant negative correlation was observed between β2* nAChR availability in the post-central gyrus or somatosensory cortex and the urge to relieve withdrawal symptoms by smoking (Staley et al. 2006).”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.1 nAChR Upregulation
What the sources say
- Supportedcites Staley et al. 2006 source
The Results section explicitly reports a significant negative correlation between β2*-nAChR availability in the postcentral gyrus or somatosensory cortex (BA 43) and the urge to smoke to relieve withdrawal symptoms. (LLM, conf=0.95)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“A reduction in basal DA levels was observed to linger for at least 5 days in mice following 12 weeks of chronic nicotine treatment (Zhang et al. 2012).”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.1 Dopaminergic System
What the sources say
- Supportedcites Zhang et al. 2012 source
The Results section, “Alterations in DA Signals After Extended Periods of Nicotine Withdrawal,” reports that after 12 weeks of nicotine treatment, baseline dopamine levels did not return to normal until 10 days after withdrawal. This supports a reduction persisting for at least 5 days in mice. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“and might impact the ability to maintain abstinence in the clinical population (Staley et al. 2006).”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.1 nAChR Upregulation
What the sources say
- Supportedcites Staley et al. 2006 source
The Discussion concludes that smokers quit in the face of increased β2*-nAChR availability and that this likely plays an important role in their ability to stay abstinent. This supports the citing sentence’s hedged claim. (LLM, conf=0.94)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“While some combinations of nAChR subunits render receptor complexes more prone to upregulation than others, desensitization is a prominent mechanism that contributes to this upregulation (Fenster et al. 1999).”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.2 Desensitization of nAChRs
What the sources say
- Supportedcites Fenster et al. 1999 source
The Conclusions state that desensitization plays an important role in upregulating receptors on the plasma membrane. This supports the citing sentence’s characterization of desensitization as a prominent contributing mechanism, while retaining the paper’s qualification that other factors matter in vivo. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Similarly, in rodents, nAChR upregulation in the dorsal hippocampus was associated with withdrawal-related deficits in hippocampal learning (Gould et al. 2012; Portugal et al. 2012).”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.1 nAChR Upregulation
What the sources say
- Partly supportedcites Gould et al. 2012 sourceExperimental — accuracy not yet measured
The Results (§3.2) report hippocampal nAChR upregulation in mice with a time course consistent with withdrawal-related deficits in contextual learning; the Discussion (§4) describes the relationship as correlational. Our copy does not localize the measured upregulation specifically to the dorsal hippocampus, so that anatomical detail is unsupported. (LLM, conf=0.85)
- Partly supportedcites Portugal et al. 2012 sourceExperimental — accuracy not yet measured
The Discussion reports that adult mice showed both hippocampal nAChR upregulation and impaired contextual fear conditioning after nicotine withdrawal; the Results (§3.5) confirm the receptor finding. The paper describes measurements in the hippocampus, not specifically the dorsal hippocampus, so that anatomical detail is unsupported. Page numbers are unavailable in our copy. (LLM, conf=0.86)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“After 2 days of abstaining from smoking, participants’ cravings were reduced only once nAChRs were again nearly saturated.”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.2 Desensitization of nAChRs
What the sources say
- Supportedcites Brody et al. 2006 source
The Methods (page not specified) describe two days of smoking and nicotine abstinence before scanning in tobacco-dependent smokers. The Results (page not specified) report that craving was reduced only with near-total nAChR occupancy: a full cigarette or smoking to satiety produced significant reductions, whereas up to a quarter of a cigarette did little despite up to 75% occupancy. (LLM, conf=0.93)
plaindirectn = 11- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Additionally, studies have demonstrated that upregulation of nAChR expression can persist for several days following termination of chronic nicotine (Pietila et al. 1998; Staley et al. 2006).”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.2 Desensitization of nAChRs
What the sources say
- Not checked — no full text of the sourcecites Pietila et al. 1998 source
- Supportedcites Staley et al. 2006 source
The Results report elevated β2*-nAChR availability after seven days of nicotine withdrawal. The Discussion describes higher brain β2*-nAChR densities in recently abstinent smokers than in nonsmokers, supporting persistence for several days after smoking cessation. (LLM, conf=0.87)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Such deficiencies in accumbal dopaminergic transmission are believed to contribute to the aversive anhedonic or dysphoric state experienced during nicotine abstinence (Koob and Le Moal 2008; Zhang et al. 2012).”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.1 Dopaminergic System
What the sources say
- Not checked — no full text of the sourcecites Koob and Le Moal 2008 source
- Supportedcites Zhang et al. 2012 source
The Discussion section, under “Alterations in Tonic and Phasic Dopamine Signals After Nicotine Withdrawal,” reports reduced dopamine release in chronically nicotine-treated mice and says this decrease may contribute to anhedonia. That supports the citing sentence’s hedged claim about a possible contribution to the aversive state during withdrawal; the paper does not establish that link as a measured clinical outcome. (LLM, conf=0.90)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“it was found that chronic smokers have more cortical, striatal, and cerebellar β2* nAChRs than non-smokers (Staley et al. 2006).”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.1 nAChR Upregulation
What the sources say
- Partly supportedcites Staley et al. 2006 sourceExperimental — accuracy not yet measured
The Discussion reports higher β2*-nAChR densities in the cortex, striatum, and cerebellum of smokers than nonsmokers, and Table 2 shows higher availability in those regions. The smokers were studied during early abstinence; the claim omits that condition and therefore implies a broader finding about chronic smokers. (LLM, conf=0.84)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“This long-lasting level of nicotine ensures that high-affinity nAChRs recurrently bind and unbind nicotine throughout the day (Picciotto et al. 2008).”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.2 Desensitization of nAChRs
What the sources say
- Partly supportedcites Picciotto et al. 2008 sourceExperimental — accuracy not yet measured
Section 1.3 reports sustained nicotine levels in chronic smokers throughout the day and says these could produce cycles of nAChR activation and desensitization. It does not establish that elevated levels ensure repeated nicotine binding and unbinding by high-affinity receptors; the same section describes potentially maintained occupancy and desensitization. No page number is available in our copy. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Furthermore, β2* nAChRs in the anterior cingulate and frontal cortex were significantly correlated with the number of days following cessation of smoking.”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.1 nAChR Upregulation
What the sources say
- Supportedcites Staley et al. 2006 source
The Results (passage 1) state that β2*-nAChR availability in the anterior cingulate and frontal cortex correlated significantly with days since the last cigarette. The Discussion (passage 3) reiterates the positive correlation. The claim's 'levels' is a reasonable paraphrase of measured receptor availability. (LLM, conf=0.93)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“This change in DA activity during withdrawal was correlated with a reduced modulatory influence by β2* nAChRs over DA release in the NAcc.”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.1 Dopaminergic System
What the sources say
- Supportedcites Zhang et al. 2012 source
The Discussion states that altered DA function after nicotine withdrawal was partly due to reduced influence of mainly β2* nAChRs over DA release in the NAc. The Results section, “High-affinity nAChRs Influence DA Release after Nicotine Withdrawal,” also reports a smaller effect of receptor blockade in withdrawn mice than in controls. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“A variety of cellular processes influence receptor upregulation (Govind et al. 2009; Rezvani et al. 2009, 2010; Henderson et al. 2014).”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.1 nAChR Upregulation
What the sources say
- Supportedcites Govind et al. 2009 source
Sections 2.2.3 and 2.3.3 describe cytokine regulation and receptor assembly and maturation as influences on nicotine-induced nAChR upregulation. Section 2.3.6 also discusses changes in receptor conformation. The supplied passages do not specify page numbers. (LLM, conf=0.94)
- Not matchedcites Rezvani et al. 2009, 2010
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Supportedcites Henderson et al. 2014 source
The Discussion describes pharmacological chaperoning, COPII-mediated ER export, and COPI-dependent Golgi–ER cycling as processes involved in nicotine-induced nAChR up-regulation. The cited paper therefore supports the broad claim that multiple cellular processes influence receptor up-regulation; page numbers are not provided in our copy. (LLM, conf=0.91)
plaindirect- Asserted: passes — The authors put it forward as true.
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The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“For example, inclusion of the α5 subunit into α4β2* nAChRs decreases the extent of desensitization (Bailey et al. 2010).”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.2 Desensitization of nAChRs
What the sources say
- Partly supportedcites Bailey et al. 2010 sourceExperimental — accuracy not yet measured
The Results section ('The α5 nicotinic subunit protects against desensitization') reports about half as much nicotine-induced desensitization in wild-type mouse layer VI neurons as in α5−/− neurons. The claim omits that cellular and exposure context; the Discussion notes that earlier work in reduced preparations found the opposite effect. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“it was found that regular smokers approach complete saturation of CNS α4β2* nAChRs throughout the day (Brody et al. 2006).”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.2 Desensitization of nAChRs
What the sources say
- Supportedcites Brody et al. 2006 source
The Results (COMMENT) state that typical daily smokers have nearly complete saturation of brain α4β2* nAChRs throughout the day, estimating 96%–98% occupancy. The Conclusions likewise say tobacco-dependent smokers maintain receptor saturation throughout the day. (LLM, conf=0.95)
plainn = 11- Asserted: passes — The authors put it forward as true.
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- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The bed nucleus of the stria terminalis (BNST), central nucleus of the amygdala (CeA), and shell of the nucleus accumbens (NAc-Sh) form the extended amygdala, an anatomically and neurochemically interconnected system located in the basal forebrain (Smith and Aston-Jones 2008).”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.4 Extended Amygdala
What the sources say
- Supportedcites Smith and Aston-Jones 2008 source
The Introduction (page not supplied) explicitly defines the extended amygdala as an anatomically and neurochemically interconnected system in the basal forebrain comprising the BNST, CeA, and NAc-Sh. (LLM, conf=0.95)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Similar deficits of contextual fear learning were observed when a nAChR antagonist (dihydro-β-erythroidine) was infused into the hippocampus of WT mice chronically treated with nicotine (Davis and Gould 2009).”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.3 Hippocampus
What the sources say
- Supportedcites Davis and Gould 2009 source
The Results section, “Intrahippocampal DHβE infusion in chronic systemic nicotine-treated β2 KO mice,” reports significantly lower contextual fear conditioning in chronically nicotine-treated WT mice given intrahippocampal DHβE than in every comparison group. This directly supports the attributed finding. (LLM, conf=0.95)
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“GABAergic inputs arrive at the VTA from the substantia nigra pars reticulata, nucleus accumbens, ventral pallidum/globus pallidus, laterodorsal tegmentum, pedunculopontine nuclei, diagonal band of Broca, bed nucleus of the stria terminalis, and the caudal tip of the VTA, termed the rostromedial tegmental nucleus (RMTg) (Geisler and Zahm 2005; Jhou et al. 2009; Kaufling et al. 2009).”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.1 Dopaminergic System
What the sources say
- Not checked — no full text of the sourcecites Geisler and Zahm 2005 source
- Partly supportedcites Jhou et al. 2009 sourceExperimental — accuracy not yet measured
The Introduction and Results identify the RMTg as a GABAergic projection to the VTA, and the Discussion (‘Anatomic specificity of RMTg function’) identifies GABAergic VTA afferents from the nucleus accumbens, ventral pallidum, and substantia nigra pars reticulata. The copy does not establish the full attributed list as GABAergic VTA inputs; in particular, it does not do so for the laterodorsal tegmentum, diagonal band of Broca, or bed nucleus of the stria terminalis. Page numbers were not available in the indexed passages. (LLM, conf=0.85)
- Not checked — no full text of the sourcecites Kaufling et al. 2009 source
plain- Asserted: passes — The authors put it forward as true.
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Every source the paper cites for this claim was checked and supports it.
In the paper
“The CRF/CRF1 receptor signaling in the CeA also mediates nicotine withdrawal-induced increases in nociceptive sensitivity in rats that are dependent on nicotine (Baiamonte et al. 2014).”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.4 Extended Amygdala
What the sources say
- Supportedcites Baiamonte et al. 2014 source
The Discussion reports that blocking CRF1 receptors in the CeA markedly attenuated withdrawal-induced thermal hyperalgesia in nicotine-dependent rats. It concludes that increased CRF/CRF1R signaling in the CeA mediates this effect. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The work also implicated β2* nAChRs in the manifestation of memory-associated deficits during nicotine withdrawal.”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.3 Hippocampus
What the sources say
- Supportedcites Davis and Gould 2009 source
The Discussion states that intrahippocampal DHβE produced withdrawal-related deficits in contextual fear conditioning in mice but not in chronic nicotine-treated β2-subunit knockout mice. It concludes that β2* nAChRs are critically involved in this learning-related deficit. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Contextual FC is dependent upon hippocampal signaling (Davis et al. 2005)”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.3 Hippocampus
What the sources say
- Supportedcites Davis et al. 2005 source
The Introduction explicitly states that contextual fear conditioning requires the hippocampus. The paper also describes it as a hippocampus-dependent association in its discussion of the findings. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“and during spontaneous withdrawal from nicotine, mice exhibit deficient contextual FC relative to saline-treated controls (Davis et al. 2005).”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.3 Hippocampus
What the sources say
- Supportedcites Davis et al. 2005 source
The Results report significantly lower contextual fear conditioning in mice withdrawn from chronic nicotine than in all other treatment groups, including saline controls. Figure 2 specifically reports less contextual freezing in nicotine-withdrawn mice given saline than in mice withdrawn from chronic saline and given saline. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Through this projection, the MHb releases acetylcholine (ACh), substance P (SP), and glutamate onto the IPN (Zhao-Shea et al. 2013).”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.2 Habenular Complex and Interpeduncular Nucleus
What the sources say
- Partly supportedcites Zhao-Shea et al. 2013 sourceExperimental — accuracy not yet measured
The Results section, “Glutamate release from MHb-IPN afferents is necessary for somatic nicotine withdrawal signs,” says that cholinergic afferents from the MHb also release glutamate into the IPN. The Discussion likewise describes cholinergic input and glutamate release, but our copy does not say that this projection releases substance P. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The best example is provided by rs16969968, the SNP that leads to an aspartic acid for an asparagine substitution (D398N) in CHRNA5 (Jackson et al. 2010).”
§ Nicotine Withdrawal > 6 Summary and Research Moving Forward
What the sources say
- Supportedcites Jackson et al. 2010 source
The passage labeled Abstract (page not provided) explicitly states that rs16969968 changes the 398th amino acid from aspartic acid to asparagine (D398N) in CHRNA5. (LLM, conf=0.95)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The impact of the mutation that defines the risk allele has been validated repeatedly in vitro and in animal models (Kuryatov et al. 2011; Morel et al. 2014).”
§ Nicotine Withdrawal > 6 Summary and Research Moving Forward
What the sources say
- Partly supportedcites Kuryatov et al. 2011 sourceExperimental — accuracy not yet measured
The Introduction identifies D398N as the risk variant, and the Results and Table 1 report functional effects measured in expressed receptors and oocytes, supporting the in vitro part of the claim. The cited paper does not report validation of this mutation in an animal model, so it does not support that part of the sentence. (LLM, conf=0.86)
- Supportedcites Morel et al. 2014 source
The Discussion (‘Dissecting the role of a human non-synonymous variant’) reports prior cell and oocyte experiments showing functional effects of the α5 risk variant. The Results report that mice expressing the variant required twice the nicotine dose for dopamine-cell activation, supporting its impact in an animal model. (LLM, conf=0.90)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“and are potential targets for treatments of the nicotine withdrawal syndrome (Grady et al. 2009).”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.2 Habenular Complex and Interpeduncular Nucleus
What the sources say
- Partly supportedcites Grady et al. 2009 sourceExperimental — accuracy not yet measured
The Discussion (Pathophysiology of α3β4* nAChR subtypes; page unavailable) links α3β4-containing receptors to addictive-drug self-administration, providing some rationale for investigating them. It does not identify α5, α3, and β4 as treatment targets for nicotine withdrawal or assess withdrawal treatments. (LLM, conf=0.78)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Furthermore, lidocaine infusion into the MHb to inhibit signaling significantly blocks the manifestations of somatic symptoms resulting from both mecamylamine-precipitated and spontaneous induction of nicotine withdrawal (Zhao-Shea et al. 2013).”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.2 Habenular Complex and Interpeduncular Nucleus
What the sources say
- Partly supportedcites Zhao-Shea et al. 2013 sourceExperimental — accuracy not yet measured
The Results section (“Glutamate release from MHb-IPN afferents is necessary for somatic nicotine withdrawal signs”; page unavailable) reports that lidocaine infusion into the MHb significantly blocked somatic signs during spontaneous withdrawal. For mecamylamine-precipitated withdrawal, it reports reduced IPN neuronal activation measured by c-Fos, not a significant reduction in somatic symptoms. (LLM, conf=0.91)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Following precipitated nicotine withdrawal in WT mice, there are elevated markers of neuronal activation in GABAergic IPN cells (Zhao-Shea et al. 2013).”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.2 Habenular Complex and Interpeduncular Nucleus
What the sources say
- Supportedcites Zhao-Shea et al. 2013 source
In Results, under “GABAergic neurons in the IPN are activated during nicotine withdrawal,” the authors report that mecamylamine-precipitated withdrawal in C57BL/6J mice significantly increased c-Fos, a marker of neuronal activation, in IPN neurons. More than 80% of the c-Fos-positive neurons in nicotine-dependent mice given mecamylamine also expressed the GABAergic marker GAD. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Administration of nicotine to mice undergoing withdrawal ameliorates this deficit (Davis et al. 2005).”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.3 Hippocampus
What the sources say
- Supportedcites Davis et al. 2005 source
The Discussion reports that an acute nicotine dose reversed the contextual fear-conditioning deficit in mice withdrawn from chronic nicotine. This directly supports the citing sentence. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Additionally, the cholinoceptive cellular population within the medial habenula (MHb) has been associated with the aversive effects of nicotine (Fowler et al. 2011).”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.2 Habenular Complex and Interpeduncular Nucleus
What the sources say
- Supportedcites Fowler et al. 2011 source
The 'Habenular α5* nAChRs control nicotine intake' section identifies α5-containing nicotinic receptors in the medial habenula–interpeduncular pathway. The 'Habenular α5* nAChRs regulate IPN activation' section links that pathway to an aversive response to high nicotine doses. Page numbers were not supplied. (LLM, conf=0.91)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Supported
In the paper
“Long-term exposure to nicotine leads to an increase, or upregulation, of nicotinebinding sites in the brain of smokers (Benwell et al. 1988)”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.1 nAChR Upregulation
What the sources say
- Not checked — no full text of the sourcecites Benwell et al. 1988 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Such polygenic contributions overlap, at least in part, with those associated with vulnerability to nicotine dependence.”
§ Nicotine Withdrawal > 1 Withdrawal Syndrome in Humans > 1.2 Genetic Influences
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Consequently, by continuing to map neuronal circuits and nAChR subpopulations that underlie the nicotine withdrawal syndrome—and by continuing to enumerate genes that predispose carriers to nicotine addiction and exacerbated withdrawal symptoms—it will be possible to pursue personalized therapeutics that more effectively treat nicotine addiction.”
§ Nicotine Withdrawal > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“the lack of α2 is sufficient to abolish somatic symptoms of precipitated nicotine withdrawal (Salas et al. 2009).”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
What the sources say
- Not checked — no full text of the sourcecites Salas et al. 2009 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The reported phenotypes likely reflect an involvement of different subtypes of β4* nAChRs.”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“β3 KO mice exhibit lower baseline levels of anxiety-related behavior in three different paradigms (Booker et al. 2007).”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
What the sources say
- Not checked — no full text of the sourcecites Booker et al. 2007 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore α6β2* nAChRs may represent viable targets for the treatment of affective symptoms experienced during nicotine withdrawal.”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“and rodents subjected to repeated nicotine administrations (Marks et al. 1983).”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.1 nAChR Upregulation
What the sources say
- Not checked — no full text of the sourcecites Marks et al. 1983 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“After at least a week of chronic nicotine administration in mice, cessation of nicotine exposure or administration of a nAChR antagonist induces affective, somatic, and cognitive signs of withdrawal (Malin et al. 1994; De Biasi and Salas 2008).”
§ Nicotine Withdrawal > 2 Withdrawal Syndrome in Mice
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“Many symptoms of nicotine withdrawal described in humans can be recapitulated in rodent models of addiction and withdrawal under experimental conditions”
§ Nicotine Withdrawal > 2 Withdrawal Syndrome in Mice
plaindirect- Asserted: passes — The authors put it forward as true.
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A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Dopaminergic deficits in the mesolimbic pathway, particularly in the nucleus accumbens, are among the neurochemical mechanisms underlying the symptoms of nicotine withdrawal (Hildebrand et al. 1998; Carboni et al. 2000; Rada et al. 2001).”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.1 Dopaminergic System
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“For example, the presence of α5 renders α4β2* nAChRs insensitive to nicotine-induced upregulation (Mao et al. 2008).”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.1 nAChR Upregulation
What the sources say
- Not checked — no full text of the sourcecites Mao et al. 2008 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The variety of nAChRs, combined with the specificity determined by afferent/efferent projections, produces the distinct neurochemistry and signaling that underlies the withdrawal syndrome.”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
In the paper
“The effects of β3 on receptor trafficking and upregulation may help explain why in the striatum α6-containing receptors without β3 are downregulated by nicotine, while those containing β3 are unaffected (Perry et al. 2007).”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.1 nAChR Upregulation
What the sources say
- Not checked — no full text of the sourcecites Perry et al. 2007 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“As nicotine has a half-life in humans of 2 h or more”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.2 Desensitization of nAChRs
What the sources say
- Not matchedcites Graham et al. 2007
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When nicotine levels are low or absent, the nAChRs recover from desensitization, leading to potentially overactive cholinergic signaling.”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.2 Desensitization of nAChRs
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Given the diversity of symptoms manifested during nicotine withdrawal, a constellation of anatomical structures is likely involved in its etiology.”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Receptors containing the β2 subunits are particularly sensitive to nicotine-induced upregulation.”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.1 nAChR Upregulation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“The presence of an accessory nAChR subunit in the receptor complex can also influence nicotine-induced upregulation.”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.1 nAChR Upregulation
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“If β4 replaces β2 subunits in either α3* or α4* nAChRs, receptor upregulation is significantly reduced (Wang et al. 1998; Sallette et al. 2004).”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.1 nAChR Upregulation
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“nicotine accumulates during a day of regular smoking to reach steady-state plasma concentrations typically ranging between 10 and 50 ng/mL (Graham et al. 2007).”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.2 Desensitization of nAChRs
What the sources say
- Not matchedcites Graham et al. 2007
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“If a withdrawal symptom exhibited by wild-type mice is absent in mice that lack functional expression of a specific nAChR subunit in a particular CNS structure, the specific subunit is likely critical to the withdrawal symptom in question.”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
In the paper
“In fact, nAChRs recover from desensitization on the scale of seconds to hours (Gentry and Lukas 2002).”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.2 Desensitization of nAChRs
What the sources say
- Not checked — no full text of the sourcecites Gentry and Lukas 2002 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“It is important to note that rates of desensitization are not necessarily equivalent across all nAChR subunit combinations.”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.2 Desensitization of nAChRs
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“This process represents a major factor in the neurobiology of nicotine withdrawal (Dani and Heinemann 1996).”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.2 Desensitization of nAChRs
What the sources say
- Not checked — no full text of the sourcecites Dani and Heinemann 1996 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“They are each densely expressed in the MHb and/or IPN (Salas et al. 2003b, 2004)”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.2 Habenular Complex and Interpeduncular Nucleus
What the sources say
- Not matchedcites Salas et al. 2003b, 2004
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The most prominent efferent output from the MHb is to the IPN via the fasciculus retroflexus, forming the MHb IPN axis.”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.2 Habenular Complex and Interpeduncular Nucleus
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“As previously discussed, the α5, α3, and β4 nAChR subunits participate in withdrawal symptomatology.”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.2 Habenular Complex and Interpeduncular Nucleus
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Considered together, these data strongly implicate the MHb-IPN circuit in the nicotine withdrawal syndrome.”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.2 Habenular Complex and Interpeduncular Nucleus
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Individuals undergoing nicotine withdrawal experience both affective and somatic symptoms beginning between 4 and 24 h after ceasing intake.”
§ Nicotine Withdrawal > 6 Summary and Research Moving Forward
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The hippocampus is a crucial structure for the manifestation of cognitive deficits during nicotine withdrawal.”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.3 Hippocampus
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 34
- Probably not a substantial claim. 15
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“α5 KO mice do not display physical symptoms associated with both spontaneous and mecamylamine-precipitated nicotine withdrawal (Salas et al. 2009) nor withdrawal-induced hyperalgesia (Jackson et al. 2008).”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
What the sources say
- Not checked — no full text of the sourcecites Salas et al. 2009 source
- Disputedcites Jackson et al. 2008 sourceExperimental — accuracy not yet measured
Jackson et al.’s Results (‘Role of the α5 nAChR Subunit in Precipitated Nicotine Withdrawal’) report significant withdrawal-induced hyperalgesia in α5 knockout mice, contrary to the part of the sentence cited to Jackson et al. The statement about spontaneous and mecamylamine-precipitated physical symptoms is cited to Salas et al. (2009), not to this source. (LLM, conf=0.95)
Checked by a reasoning model — may be wrong.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) reports 7 primary symptoms associated with nicotine withdrawal: irritability/anger/frustration, anxiety, depressed mood, difficulty concentrating, increased appetite, insomnia, and restlessness (American Psychiatric Association 2013).”
§ Nicotine Withdrawal > 1 Withdrawal Syndrome in Humans > 1.1 Symptoms
What the sources say
- Could not verifycites American Psychiatric Association 2013 sourceExperimental — accuracy not yet measured
The indexed passages under “Symptoms and patterns” (11 September 2026; no page given) describe depressive episodes, not nicotine withdrawal. Searches for the seven listed symptoms and for tobacco-withdrawal diagnostic symptoms found no passage that verifies the DSM-5 list or its count. (LLM, conf=0.78)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Genetic factors may also account for 29–53 % of the variance in withdrawal symptoms and approximately 50 % of the variance in quitting success (Xian et al. 2003, 2005; Pergadia et al. 2006).”
§ Nicotine Withdrawal > 1 Withdrawal Syndrome in Humans > 1.2 Genetic Influences
What the sources say
- Not checked — no full text of the sourcecites Xian et al. 2003 source
- Supportedcites Xian et al. 2005 source
The Four-class nicotine withdrawal section reports that genetics accounted for 31.0% of variance in the withdrawal phenotype, within the cited range, and 50.6% of variance in failed cessation. The paper measures failed cessation rather than 'quitting success,' but its estimate supports the sentence's approximate figure for quitting outcomes. (LLM, conf=0.88)
- Partly supportedcites Pergadia et al. 2006 sourceExperimental — accuracy not yet measured
The Abstract reports 29% and 53% heritability for depressed mood during withdrawal in women and men, respectively, but gives 26–43% for most other symptoms and 9% for decreased heart rate. The paper does not report that genetic factors explain approximately 50% of variance in quitting success; its Introduction discusses cessation failure without that estimate. Page numbers are unavailable in our copy. (LLM, conf=0.86)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“α2 KO mice exhibit more somatic symptoms of withdrawal in novel environments (Lotfipour et al. 2013), but display no somatic signs of withdrawal in habituated environments (i.e., the home cage) (Salas et al. 2009).”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
What the sources say
- Supportedcites Lotfipour et al. 2013 source
The Results section reports enhanced somatic nicotine-withdrawal behaviors in Chrna2−/− mice versus wild-type controls in a novel environment. The Discussion likewise says the knockout mice showed more paw tremors, head shakes, backing, and curls there. The home-cage clause is separately attributed to Salas et al. (2009), so it is not part of the claim judged against this citation. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites Salas et al. 2009 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“β4 KO mice exhibit no somatic signs of nicotine withdrawal or hyperalgesia following mecamylamine-induced withdrawal (Salas et al. 2004).”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
What the sources say
- Partly supportedcites Salas et al. 2004 sourceExperimental — accuracy not yet measured
The Results section reports fewer somatic signs in nicotine-treated β4 knockout mice after mecamylamine, not no signs. It also reports no hyperalgesia in β4 knockout mice, but the Animals section specifies that the hyperalgesia tests were performed after interruption of nicotine infusion, rather than after mecamylamine-precipitated withdrawal. Page numbers are not provided in the supplied copy. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“behaviors that are controlled, at least in part, by nigrostriatal and mesolimbic dopaminergic activity (Cui et al. 2003)”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
What the sources say
- Supportedcites Cui et al. 2003 source
The Introduction states that locomotor activity is regulated in part by nigrostriatal dopaminergic neurotransmission and prepulse inhibition of acoustic startle by mesolimbic dopaminergic transmission. This directly supports the attributed claim. (LLM, conf=0.95)
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“β2 KO mice exhibit levels of somatic signs of withdrawal and abstinence-induced hyperalgesia comparable to those of WT mice (Salas et al. 2004).”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
What the sources say
- Partly supportedcites Salas et al. 2004 sourceExperimental — accuracy not yet measured
The Results section reports that β2 knockout mice had somatic withdrawal scores similar to nicotine-treated controls after mecamylamine injection. Its hyperalgesia results compare wild-type mice with β4 knockout mice, not β2 knockout mice, so the claimed comparison of abstinence-induced hyperalgesia is not supported (page not specified in our copy). (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“α3β4* nAChRs are the most likely contributors to physical components of withdrawal given the high levels of expression of α3 and β4 mRNA in the MHb, and the fact that the α3β4-selective α-conotoxin AuIB blocks the emergence of somatic signs of withdrawal (Jackson et al. 2013).”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
What the sources say
- Partly supportedcites Jackson et al. 2013 sourceExperimental — accuracy not yet measured
The Results (section 3.4; page unavailable) report that AuIB dose-dependently reduced somatic signs of nicotine withdrawal, and the Discussion (section 4; page unavailable) links α3β4* receptors to physical withdrawal and notes high α3 and β4 subunit expression in the MHb. The copy does not specify that this expression is mRNA expression, and it says α5 receptors also mediate somatic signs; it therefore does not establish α3β4* receptors as the most likely contributors relative to other receptors. (LLM, conf=0.84)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“As reported for the α5 KO mice (Gangitano et al. 2009), β3 KO mice have altered hypothalamic pituitary adrenal axis responses (Booker et al. 2007).”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
What the sources say
- Supportedcites Gangitano et al. 2009 source
The Results section (page not supplied) reports lower basal plasma corticosterone in female α5 knockout mice and higher basal hypothalamic CRF in male α5 knockout mice. These findings support the α5 comparison attributed to Gangitano et al.; the β3 finding is attributed to a different source. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites Booker et al. 2007 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Changes were also reported for locomotor activity and prepulse inhibition of acoustic startle”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
What the sources say
- Supportedcites Cui et al. 2003 source
The Behavioral analysis section reports that β3 knockout mice had significantly higher open-field activity and significantly less prepulse inhibition of acoustic startle than wild-type littermates. The Behavioral effects of β3 deletion section summarizes both changes. (LLM, conf=0.95)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“a non-nicotine pharmaceutical currently FDA approved for the treatment of smoking cessation, varenicline, acts as a partial agonist at α6β2* nAChRs (Grady et al. 2010; Bordia et al. 2012).”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
What the sources say
- Supportedcites Grady et al. 2010 source
The Discussion (page not available) explicitly reports that varenicline is a partial agonist at α6β2*-nAChRs and describes it as marketed for smoking cessation. The paper does not specifically state its FDA approval status, but directly supports the pharmacological claim for which it is cited. (LLM, conf=0.92)
- Supportedcites Bordia et al. 2012 source
The Introduction identifies varenicline as an FDA-approved drug used to help people quit smoking and states that this study found it to be a partial agonist at α6β2* nAChRs in rat and monkey striatum. The Discussion likewise reports its lower efficacy than nicotine at these receptors in both species. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“There was no influence on the somatic symptoms of withdrawal, suggesting a selective role for α6 nAChR subunits in the affective manifestations of withdrawal (Jackson et al. 2009).”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
What the sources say
- Supportedcites Jackson et al. 2009 source
The Discussion reports that an α6-selective antagonist blocked anxiety-related behavior and conditioned place aversion during nicotine withdrawal, but had no effect on somatic signs. The authors identify this as a role for α6-containing receptors in affective, but not physical, withdrawal. (LLM, conf=0.94)
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“While the DAergic VTA has been widely implicated in the rewarding aspects of addictive drugs, it has also been shown to participate in the signaling of aversion and lack of expected reward (Schultz et al. 1998; Ungless et al. 2004; Tobler et al. 2007; De Biasi and Dani 2011).”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.1 Dopaminergic System
What the sources say
- Not checked — no full text of the sourcecites Schultz et al. 1998 source
- Not checked — no full text of the sourcecites Ungless et al. 2004 source
- Partly supportedcites Tobler et al. 2007 sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) says dopamine-neuron responses are stronger for cues predicting greater reward, supporting a general role in reward signaling. It does not establish that the VTA signals aversion or the absence of an expected reward, or address the rewarding effects of addictive drugs. (LLM, conf=0.81)
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“It has been suggested that receptor desensitization may be a major contributor to the upregulation observed in chronic users of nicotine-containing products (Benowitz 2008).”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.2 Desensitization of nAChRs
What the sources say
- Supportedcites Benowitz 2008 source
The Biology of Nicotine Reinforcement (p. 4) says that repeated nicotine exposure increases brain nicotinic receptors and that this upregulation is believed to occur in response to nicotine-mediated receptor desensitization. The claim preserves the paper’s tentative framing. (LLM, conf=0.90)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Furthermore, chronic nicotine treatment upregulated a variety of nAChRs in the hippocampus, and the duration of β2 subunit upregulation relative to other nAChR subunits most closely corresponded to the total duration of memory-associated withdrawal symptoms (Gould et al. 2012).”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.3 Hippocampus
What the sources say
- Partly supportedcites Gould et al. 2012 sourceExperimental — accuracy not yet measured
Results §3.2 (page unavailable) reports increased hippocampal cytisine-sensitive binding, associated with α4β2* receptors, on a time course similar to the contextual-learning withdrawal deficit. It found no increase in hippocampal cytisine-resistant binding; Results §3.3 found no increase in β2 subunit mRNA. The paper therefore supports a relationship involving β2-containing receptors, not the claim that various hippocampal receptor types were upregulated or that β2 subunit upregulation was compared with other subunits. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“This effect was not attributable simply to a lowered threshold of fear responses inherent to the effects of nicotine because cued FC was equivalent between nicotine-treated and nicotine-naïve groups.”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.3 Hippocampus
What the sources say
- Supportedcites Davis et al. 2005 source
The Results report impaired contextual fear conditioning during withdrawal but no differences among groups in cued fear conditioning (Figure 1; Results). The discussion accompanying Figure 2 says these findings suggest nicotine does not increase fear in general, supporting the claim that a general change in fear responses does not explain the contextual effect. (LLM, conf=0.92)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Nicotine withdrawal leads to an increase in CRF in the CeA, and blockade of CRF1 receptors diminishes nicotine withdrawalinduced anxiety-like behavior (George et al. 2007).”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.4 Extended Amygdala
What the sources say
- Supportedcites George et al. 2007 source
The Results report that mecamylamine-precipitated withdrawal increased CRF in the central nucleus of the amygdala in nicotine-dependent rats. They also report that a CRF1 receptor antagonist blocked the withdrawal-induced increase in defensive burying, a measure of anxiety-like behavior. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The MHb also hosts the expression of norepinephrine (NE), serotonin, ATP, and several neuropeptides (Dao et al. 2014).”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.2 Habenular Complex and Interpeduncular Nucleus
What the sources say
- Supportedcites Dao et al. 2014 source
The section “Neurokinins participate in the nicotine-induced enhancement of excitability in the MHb” explicitly lists norepinephrine, serotonin, ATP, and numerous neuropeptides as expressed in the MHb. The excerpt does not indicate a page number. (LLM, conf=0.95)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The LHb sends excitatory glutamatergic projections to the RMTg and is a major component of the circuit underlying negative reward (Dani and De Biasi 2013).”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.2 Habenular Complex and Interpeduncular Nucleus
What the sources say
- Supportedcites Dani and De Biasi 2013 source
In “THE DOPAMINE SYSTEMS” (page not provided), the paper describes excitatory glutamatergic projections from the LHb to the RMTg. It also says this connection strongly influences dopamine activity and reward prediction, with LHb activity increasing when an expected reward is omitted—supporting its described role in negative reward processing. (LLM, conf=0.91)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Additionally, infusion of an α3β4* nAChR-selective antagonist into the IPN elicited somatic withdrawal signs in nicotine-naïve mice and an even greater number of total symptoms in mice chronically treated with nicotine (Zhao-Shea et al. 2013).”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.2 Habenular Complex and Interpeduncular Nucleus
What the sources say
- Supportedcites Zhao-Shea et al. 2013 source
The Results section on β4 nAChR blockade (page not available) reports that IPN infusion of SR16584 induced withdrawal-like symptoms in nicotine-naïve mice and more total symptoms in chronically nicotine-treated mice. The paper describes SR16584 as selective for β4-containing nAChRs and cites a study of α3β4-selective ligands. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Activity in the RMTg increases upon exposure to aversive stimuli and decreases upon exposure to reward stimuli, representing inversely correlated signaling patterns (Hong et al. 2011).”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.1 Dopaminergic System
What the sources say
- Partly supportedcites Hong et al. 2011 sourceExperimental — accuracy not yet measured
The Results (‘Reward-related properties of primate RMTg neurons’; page not provided) report that reward-negative neurons increased activity when an expected reward was absent and decreased activity when an unexpected reward occurred. The paper also reports reward-positive neurons with the opposite pattern. It supports inverse responses to reward versus non-reward in a subset of RMTg neurons, but does not establish the claimed response to aversive stimuli generally. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The habenular complex, comprising the lateral (LHb) and medial (MHb) nuclei, is a diencephalic, epithalamic structure located ventrally along the dorsal third ventricle (Dani and De Biasi 2013).”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.2 Habenular Complex and Interpeduncular Nucleus
What the sources say
- Partly supportedcites Dani and De Biasi 2013 sourceExperimental — accuracy not yet measured
The Dopamine Systems section says the lateral and medial habenula form the habenula complex, an epithalamic structure by the third ventricle. It does not specify that the complex lies ventrally along the dorsal third ventricle; that more precise location is unsupported by this passage. No page number is provided in our copy. (LLM, conf=0.86)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Currently, the literature suggests that multiple genetic loci influence the severity of withdrawal symptoms and the ability to abstain from smoking.”
§ Nicotine Withdrawal > 1 Withdrawal Syndrome in Humans > 1.2 Genetic Influences
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Indeed, a transgenic mouse model that overexpresses β4 nAChR subunits exhibits altered nicotine consumption and CPA (Frahm et al. 2011)”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
What the sources say
- Not checked — no full text of the sourcecites Frahm et al. 2011 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The MHb/IPN pathway plays a crucial role in mediating the physical manifestations of nicotine withdrawal and is the likely location of the effects of α5-containing nAChR on this phenotype (Salas et al. 2009).”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
What the sources say
- Not checked — no full text of the sourcecites Salas et al. 2009 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Because AuIB does not interfere with the affective symptomatology of withdrawal in the EPM and CPA paradigms, α6β4* nAChRs might be involved.”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The withdrawal syndrome exhibited can be alleviated by nicotine administration—akin to nicotine replacement strategies such as nicotine patches or gum—or by administration of pharmacological agents used as cessation aids in humans, such as bupropion or varenicline (Rennard and Daughton 2014).”
§ Nicotine Withdrawal > 2 Withdrawal Syndrome in Mice
What the sources say
- Not checked — no full text of the sourcecites Rennard and Daughton 2014 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, these results suggest participation of β2 nAChR subunits in the signaling responsible for affective, but not somatic, symptoms of nicotine withdrawal.”
§ Nicotine Withdrawal > 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms > 3.1 Insight from nAChR Subunit KO Mice
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Conversely, co-expression of β3 increases α6β2 and α6β4 receptor levels and enhances nicotine-induced upregulation of α6β2β3 receptors compared to α6β2 receptors (Tumkosit et al. 2006).”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.1 nAChR Upregulation
What the sources say
- Not checked — no full text of the sourcecites Tumkosit et al. 2006 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Thus far, several brain structures have been already implicated in the withdrawal syndrome.”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Different anatomical structures in the CNS express distinct populations of nAChRs.”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Accordingly, as the rates of desensitization and recovery from receptor upregulation during nicotine withdrawal are incongruent, a physiological landscape is established in which there are more receptors expressed than would be present in nicotine-naïve individuals, and these receptors are less responsive to agonist binding.”
§ Nicotine Withdrawal > 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome > 4.2 Desensitization of nAChRs
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The mesocorticolimbic dopamine (DA) system has been identified as critical to the development of addictive behaviors, and DA signaling is involved in reward-based reinforcement of drug-derived behaviors.”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.1 Dopaminergic System
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Candidate SNPs can have a multitude of biochemical functions, such as altering DNA methylation, histone modification, or accessibility of DNA to transcription factor binding that can impact when, where, and how much a gene, and its protein, is expressed.”
§ Nicotine Withdrawal > 6 Summary and Research Moving Forward
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The syndrome is most severe in the first week, but it can persist for longer periods of time.”
§ Nicotine Withdrawal > 6 Summary and Research Moving Forward
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Increasing attention is being paid to the functional analysis of rare variants, as common variants can explain only a small percentage of the variance in smoking-related phenotypes.”
§ Nicotine Withdrawal > 6 Summary and Research Moving Forward
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“Mice chronically treated with nicotine exhibit symptoms of withdrawal upon microinjection of mecamylamine into the MHb and IPN, but fail to manifest withdrawal symptoms when mecamylamine is injected to the cortex, hippocampus, or VTA (Salas et al. 2009).”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.2 Habenular Complex and Interpeduncular Nucleus
What the sources say
- Not checked — no full text of the sourcecites Salas et al. 2009 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The habenula has been demonstrated to participate in the signaling underlying fear, anxiety, depression, and stress (Viswanath et al. 2013).”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.2 Habenular Complex and Interpeduncular Nucleus
What the sources say
- Not matchedcites Viswanath et al. 2013
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The system has been implicated in stress-related components of drug withdrawal and is a site of interaction between corticotropinreleasing factor (CRF) and NE transmission.”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.4 Extended Amygdala
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The IPN is located in the ventral midbrain, with the VTA and median raphe nucleus located dorsally.”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.2 Habenular Complex and Interpeduncular Nucleus
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Given the polygenic nature of nicotine addiction, many other mechanisms and many other brain areas are likely to influence the manifestations of withdrawal.”
§ Nicotine Withdrawal > 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal > 5.4 Extended Amygdala
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
- Rests on an assumption: Nicotine addiction is polygenic.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“More work is necessary at the bench and in the clinic, as a collection of genes likely operates collectively to predispose or protect individuals to or from nicotine addiction and withdrawal.”
§ Nicotine Withdrawal > 6 Summary and Research Moving Forward
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“During this time, relapse is incentivized by the ability of nicotine to alleviate or abolish withdrawal symptoms.”
§ Nicotine Withdrawal > 6 Summary and Research Moving Forward
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Genetic studies of nicotine dependence and smoking cessation have identified several risk factors using GWAS, candidate gene approaches, and pharmacogenetic analyses.”
§ Nicotine Withdrawal > 6 Summary and Research Moving Forward
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“For many of the SNPs, however, there is no change in protein sequence, and therefore, it is harder to formulate clear functional hypothesis.”
§ Nicotine Withdrawal > 6 Summary and Research Moving Forward
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“In addition, there are cognitive deficits that manifest during nicotine withdrawal, including difficulty concentrating, increased reaction times in tasks requiring sustained attention, and impaired episodic and working memory (Myers et al. 2008; Wesnes et al. 2013).”
§ Nicotine Withdrawal > 6 Summary and Research Moving Forward
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
Nicotine withdrawal begins 4–24 hours after stopping chronic nicotine product use, peaks around the third day, and then declines over the following 3–4 weeks.
“An aversive abstinence syndrome manifests 4–24 h following cessation of chronic use of nicotine-containing products. Symptoms peak on approximately the 3rd day and taper off over the course of the following 3–4 weeks.”
The paper relies on this without support.
How nicotine is consumed is the main determinant of how severe withdrawal symptoms will be.
“While the severity of withdrawal symptoms is largely determined by how nicotine is consumed”
The paper relies on this without support.
No preclinical data exist on how the β3 null mutation affects nicotine-related behavior.
“no preclinical data are available on the effects of the β3 null mutation on nicotine-related behavior.”
The paper relies on this without support.
Nicotine addiction is polygenic.
“Given the polygenic nature of nicotine addiction”
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?
The cited source says what the claim attributes to it.
In the citing paper
“Nicotine withdrawal symptoms may also be accompanied by depressed mood in some individuals.14”
From Are smoking cessation treatments associated with suicidality risk? An overview (2016) · cites this paper as [14]
Citations
Cites
Diagnostic and Statistical Manual of Mental Disorders
American Psychiatric Association (2013) · doi:10.1176/appi.books.9780890425596 · Cited by 116,369
Neurodegenerative Disorders: Parkinson's Disease and Huntington's Disease
Hague, S., Klaffke, S., & Bandmann, O. (2006) · IMPERIAL COLLEGE PRESS eBooks · doi:10.1142/9781860948961_0007 · Cited by 2,767
Optogenetics in neural systems
Yizhar, O., Fenno, L. E., Davidson, T. J., Mogri, M., & Deisseroth, K. (2011) · Neuron · doi:10.1016/j.neuron.2011.06.004 · Cited by 1,881
Assessing antidepressant activity in rodents: recent developments and future needs
Cryan, J. F., Markou, A., & Lucki, I. (2002) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(02)02017-5 · Cited by 1,551 · cited 1×
“The emergence of depression-like symptoms during withdrawal can be assessed with the forced swim test (FST), which assesses learned helplessness by monitoring passive coping strategies such as immobility (Cryan et al. 2002; Thanos et al. 2013).”
BackgroundAddiction and the brain antireward system
Koob, G. F., & Le Moal, M. (2008) · Annual Review of Psychology · doi:10.1146/annurev.psych.59.103006.093548 · Cited by 1,457
Crawley, J. N., Belknap, J. K., Collins, A. C., Crabbe, J. C., Frankel, W. N., Henderson, N. D., HITZEMANN, R. J., Maxson, S. C., Miner, L. L., Silva, A. J., et al. (1997) · Psychopharmacology · doi:10.1007/s002130050327 · Cited by 1,389 · cited 3×
“The EPM consists of two enclosed arms with walls running along their periphery, and two open arms with no walls that present an environment resembling elevated cliffs (Crawley et al. 1997).”
BackgroundInfluentialThe 5-choice serial reaction time task: behavioural pharmacology and functional neurochemistry
Robbins, T. (2002) · Psychopharmacology · doi:10.1007/s00213-002-1154-7 · Cited by 1,282 · cited 1×
“The five-choice serial reaction time task (5-CSRTT), also called operant signal detection, is a behavioral test used to characterize the effects of treatments on sustained and divided attention (Robbins 2002).”
MethodGenome-wide meta-analyses identify multiple loci associated with smoking behavior
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Uniform Inhibition of Dopamine Neurons in the Ventral Tegmental Area by Aversive Stimuli
Ungless, M. A., Magill, P. J., & Bolam, J. P. (2004) · Science · doi:10.1126/science.1093360 · Cited by 782 · cited 1×
“While the DAergic VTA has been widely implicated in the rewarding aspects of addictive drugs, it has also been shown to participate in the signaling of aversion and lack of expected reward (Schultz et al. 1998; Ungless et al. 2004; Tobler et al. 2007; De Biasi and Dani 2011).”
BackgroundJhou, T. C., Fields, H. L., Baxter, M. G., Saper, C. B., & Holland, P. C. (2009) · Neuron · doi:10.1016/j.neuron.2009.02.001 · Cited by 696 · cited 1×
“…accumbens, ventral pallidum/globus pallidus, laterodorsal tegmentum, pedunculopontine nuclei, diagonal band of Broca, bed nucleus of the stria terminalis, and the caudal tip of the VTA, termed the rostromedial tegmental nucleus (RMTg) (Geisler and Zahm 2005; Jhou et al. 2009; Kaufling et al. 2009).”
Background
Research works printed but not linked: 1
- Graham AW, Schultz TK, Mayo-Smith MF, Ries RK, Wilford B (2007) Principles of addiction medicine. Lippincott Williams & Wilkins, Philadelphia
Cited by
Sorted by citations
McLaughlin, I., Dani, J. A., & Biasi, M. D. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.14008 · Cited by 231
Self-citationDelay discounting of different outcomes: Review and theory
Odum, A. L., Becker, R. J., Haynes, J. M., Galizio, A., Frye, C. C. J., Downey, H., Friedel, J. E., & Pérez, D. M. (2020) · Journal of the Experimental Analysis of Behavior · doi:10.1002/jeab.589 · Cited by 207
“…to change behavior, such as to help people overcome addiction, many of the rewards for changing behavior are delayed (e.g., better health after quitting smoking) and opposed by immediate punishers (e.g., anxiety, difficulty concentrating, insomnia, irritability; see McLaughlin et al., 2015).”
BackgroundE-Cigarettes are More Addictive than Traditional Cigarettes—A Study in Highly Educated Young People
Jankowski, M., Krzystanek, M., Zejda, J. E., Majek, P., Lubański, J., Lawson, J. A., & Brożek, G. M. (2019) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph16132279 · Cited by 184
“Nicotine withdrawal effects such as irritability, anxiety, poor concentration, memory impairment, and insomnia can occur after cessation of chronic nicotine use [3].”
BackgroundDopaminergic and cholinergic learning mechanisms in nicotine addiction
Subramaniyan, M., & Dani, J. A. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12871 · Cited by 110
Self-citationUnderstanding the habenula: A major node in circuits regulating emotion and motivation
Ables, J. L., Park, K., & Ibáñez-Tallon, I. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106734 · Cited by 79
Metadata
- Authors
- McLaughlin, I., Dani, J. A., & De Biasi, M.
- Affiliations
- University of Pennsylvania (US)
- ORCID
- Dani, John A.
- Venue
- Current Topics in Behavioral Neurosciences
- Publisher
- Springer International Publishing
- Published
- 2015
- Volume
- 24
- Pages
- 99-123
- ISSN
- 1866-3370 (ISSN-L)
- 1866-3389
- PMC
- PMC4542051
- OpenAlex
- W4211219695
- Semantic Scholar
- 1619d9e91fe0ea0e965cfd014a9599bd86d8925d
- Cited by
- 191
- References
- 140
- Citations by year
- 2026: 18 · 2025: 37 · 2024: 21 · 2023: 34 · 2022: 13 · 2021: 20 · 2020: 24 · 2019: 5 · 2018: 8 · 2017: 5 · 2016: 3 · 2015: 3
- FWCI
- 35.56
- Type
- book chapter
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Current topics in behavioral neurosciences (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (R21DA024385, R01DA009411, R01DA036572, T32DA028874)
- National Cancer Institute (U19CA148127)
- National Institute of Neurological Disorders and Stroke (R01NS021229)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › 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
- nicotine withdrawal, nicotine dependence, single nucleotide polymorphisms, nicotinic acetylcholine receptors, nAChR subunits, neural circuits, transgenic mouse model, personalized treatment, smoking cessation
- MeSH terms
- Animals, Brain, Humans, Nicotine, Receptors, Nicotinic, Substance Withdrawal Syndrome
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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