Enhanced vulnerability to the rewarding effects of nicotine during the adolescent period of development
Open accessAbstract
This study compared the rewarding and aversive effects of nicotine in adolescent, adult, and adult rats preexposed to nicotine during adolescence. Prior to conditioning, the rats were tested for their initial preference for either of 2 distinct compartments. Adolescent and adult rats then received various nicotine doses in their initially non-preferred side on one day and saline in the other side on alternate days. This 2-day procedure was repeated over 8 consecutive days. Following conditioning, rats were re-tested for their preference. Another cohort of adolescent and adult rats were conditioned with various doses of D-amphetamine. Nicotine produced CPP in an inverted U-shaped manner in both age groups. However, adolescents displayed a larger upward shift in CPP that was significant across a wider dose range relative to adults. There were no developmental differences to CPP produced by D-amphetamine. In a final study, adolescents were prepared with pumps that delivered nicotine for 14 days. These rats were conditioned later as adults using the same procedures used previously. Pre-exposure to nicotine during adolescence diminished the aversive effects produced by the highest nicotine dose in naive adults. Taken together, these studies provide a basis for enhanced vulnerability to nicotine during adolescence.
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The acute nicotine effect was much larger in adults than in adolescents, which does not explain the increased sensitivity of adolescents to nicotine.
“In addition, the acute nicotine effect was much larger in adults than in adolescents, thereby not explaining the increased sensitivity of adolescents for nicotine (25, 45).”
From Adolescent nicotine exposure transiently increases high-affinity nicotinic receptors and modulates inhibitory synaptic transmission in rat medial prefrontal cortex (2012) · cites this paper as [45]
The Results (section 3; page unavailable) report an approximately twofold larger nicotine-induced preference response in adolescent than adult rats, the opposite of the claimed age comparison. The Introduction (section 1; page unavailable) also reports that a single nicotine injection produced conditioned place preference in adolescents but not adults. The paper does not conclude that a larger acute effect in adults fails to explain adolescent sensitivity. (LLM, conf=0.86)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredAdolescent nicotine exposure increases later nicotine reward and reduces nicotine aversion in adult animals.
“Adolescent nicotine treatment increases subsequent nicotine reward and decreases aversion in adults”
From Unique, long-term effects of nicotine on adolescent brain. (2020) · cites this paper as Torres et al., 2008
The Discussion reports that adult rats exposed to nicotine during adolescence did not show the aversion seen at the highest dose in naïve adults. But it also says those rats did not show increased nicotine reward: their dose-response curve was relatively flat, and adolescent exposure did not facilitate conditioned place preference in adulthood. (LLM, conf=0.90)
Experimental — accuracy not yet measuredAdolescent rodents are more sensitive than adults to the acute rewarding effects of nicotine, as shown by conditioned place preference, with some studies demonstrating reward after a single pairing of drug and context.
“Adolescent rodents are more sensitive than adults to the acute rewarding effects of nicotine, as shown by conditioned place preference [133–138], with some studies demonstrating reward after a single pairing of drug and context [139,140].”
From Nicotine on the developing brain. (2023) · cites this paper as [136]
Adolescent rats are often less sensitive than adults to aversive properties of both non-drug and drug stimuli, with drug effects emerging at higher doses of the same drugs that at lower doses they find more reinforcing than adults.
“For instance, adolescent rats are often less sensitive than adults to aversive properties of both non-drug and drug stimuli, with the latter emerging at higher doses of the same drugs that, at lower doses, they conversely find more reinforcing than adults (cocaine, amphetamine, nicotine and alcohol)(38; 60; 61).”
From Adolescent Neurodevelopment (2013) · cites this paper as [60]
Adolescent rats are less sensitive than adult rats to the aversive effects of various drugs in conditioned taste aversion.
“Adolescent rats, for instance, have often been found to be less sensitive than their adult counterparts to the aversive effects of a variety of drugs when indexed via conditioned taste aversions (CTA)”
From Rewards, aversions and affect in adolescence: emerging convergences across laboratory animal and human data (2011) · cites this paper as Torres et al, 2008
The converse age-related sensitivities to rewarding and aversive stimuli are unlikely to reflect age differences in capacity to express classical conditioning.
“Many of these converse age-related sensitivities to rewarding and aversive stimuli have been revealed using similar place or taste conditioning procedures (sometimes even within the same study – e.g., see Torres et al, 2008), and hence are unlikely to reflect any potential age differences in capacity to express classical conditioning.”
From Rewards, aversions and affect in adolescence: emerging convergences across laboratory animal and human data (2011) · cites this paper as Torres et al, 2008
Adolescent rats are often less sensitive than adult rats to aversive effects of various drugs as indexed by conditioned taste aversions.
“Adolescent rats, for instance, have often been found to be less sensitive than their adult counterparts to the aversive effects of a variety of drugs when indexed via conditioned taste aversions (CTA)”
From Rewards, aversions and affect in adolescence: emerging convergences across laboratory animal and human data (2011) · cites this paper as Torres et al, 2008
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- Authors
- TORRES, O., TEJEDA, H., NATIVIDAD, L., & ODELL, L.
- Affiliations
- The University of Texas at El Paso (US)
- Corresponding author
- ODELL, L
- Venue
- Pharmacology Biochemistry and Behavior
- Publisher
- Elsevier BV
- Published
- 2008-10
- Volume
- 90
- Issue
- 4
- Pages
- 658-663
- ISSN
- 0091-3057 (ISSN-L)
- PMC
- PMC2576495
- OpenAlex
- W2101673955
- Cited by
- 169
- References
- 38
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 6 · 2023: 8 · 2022: 5 · 2021: 7 · 2020: 7 · 2019: 6 · 2018: 13 · 2017: 7 · 2016: 17 · 2015: 14 · 2014: 10 · 2013: 19 · 2012: 8
- FWCI
- 7.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Pharmacology Biochemistry and Behavior (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Drug Abuse (F31DA021133, R01DA021274, R25DA033613)
- National Institute of General Medical Sciences (R25GM055036)
- National Center for Research Resources (G12RR008124)
- Topics
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- nicotine, adolescent development, nicotine reward, conditioned place preference, developmental vulnerability, amphetamine, nicotine self-administration
- MeSH terms
- Aging, Central Nervous System Stimulants, Analysis of Variance, Animals, Conditioning, Operant, Dextroamphetamine, Dose-Response Relationship, Drug, Environment, Male, Nicotine, Reward, Rats, Wistar, Nicotinic Agonists, Rats
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