Sex differences in conditioned nicotine reward are age-specific
Open accessAbstract
Women constitute half of all smokers and many studies suggest that adult males and females differ in factors that maintain tobacco smoking, yet there is limited information about sex differences in nicotine reward during adolescence. Limited studies suggest that adolescent male rats self-administer more nicotine than adults, suggesting that drug administration during adolescence leads to different behavioral effects than during adulthood. In the present study, male rats developed a significant conditioned place preference (CPP) to lower doses of nicotine than females, regardless of age. In addition, adolescents were more sensitive than adults. In female rats, adolescents exhibited a CPP of greater magnitude than adult females. In males, the magnitude of the CPP did not differ as a function of age, but adolescents exhibited CPP to lower doses than adults. There also were differences in nicotinic acetylcholinergic receptor binding in nucleus accumbens and caudate putamen in response to nicotine across age and sex. These findings suggest that it is necessary to consider sex- and age-specific effects of drugs such as nicotine when developing strategies for improving smoking cessation treatments.
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Adolescents of both sexes show stronger conditioned place preference (CPP) than adults following nicotine injections.
“adolescents of both sexes show stronger conditioned place preference (CPP) than adults following nicotine injections [190]”
From Consequences of adolescent drug use (2023) · cites this paper as [190]
The Results (§3.1) report higher nicotine CPP in adolescent than adult female rats at 0.4 and 0.6 mg/kg. Adolescent males showed CPP at a lower dose than adult males (0.05 mg/kg), but both ages showed CPP at 0.1 and 0.2 mg/kg. The paper therefore supports an age difference in both sexes, not an unqualified claim that adolescents of both sexes show stronger CPP. (LLM, conf=0.88)
Experimental — accuracy not yet measuredSex differences in nicotine sensitivity at different phases of adolescence have been reported in preclinical studies.
“Sex differences in nicotine sensitivity at different phases of adolescence have also been reported in preclinical studies (Cao et al. 2010; Kawai et al. 2011; Lenoir et al. 2015), and are consistent with clinical observations of differing developmental trajectories of tobacco use in males and females (Chen & Jacobsen, 2012).”
From <scp>N</scp> icotine and the adolescent brain (2015) · cites this paper as Lenoir et al. 2015
The Results (§3.1) report sex differences in nicotine conditioned place preference in periadolescent rats: males responded to lower doses than females. But the Methods (§2.1) identify only one adolescent age group, starting at postnatal day 34, alongside an adult group. This paper therefore supports sex differences during periadolescence, not a comparison across different phases of adolescence. (LLM, conf=0.85)
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 [138]
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<scp>N</scp> icotine and the adolescent brain
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Consequences of adolescent drug use
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“…release in the NAc shell (NAcSh) and NAc core of adolescents relative to adults [189] and adolescents of both sexes show stronger conditioned place preference (CPP) than adults following nicotine injections [190], as well as enhanced locomotor activity following nicotine self-administration [191].”
BackgroundUnique, long-term effects of nicotine on adolescent brain.
Leslie, F. M. (2020) · Pharmacology, Biochemistry, and Behavior · doi:10.1016/j.pbb.2020.173010 · Cited by 178 · see citing works
“Whereas adults of both sexes experience aversive effects of high doses of nicotine, adolescents tolerate the drug well (Adriani et al., 2002; Shram et al., 2006; Torres et al., 2008, 2009; Lenoir et al., 2015).”
BackgroundStress is a principal factor that promotes tobacco use in females
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Nicotine on the developing brain.
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“Although the sex effects did not reach significance in the current study, this should be explored further, particularly as sex differences have been found in the rewarding effects of nicotine (Lenoir et al., 2015).”
BackgroundXue, S., Behnood-Rod, A., Wilson, R., Wilks, I., Tan, S., & Bruijnzeel, A. W. (2020) · Nicotine & Tobacco Research · doi:10.1093/ntr/nty249 · Cited by 38 · see citing works
Adolescent Rats Self-Administer Less Nicotine Than Adults at Low Doses
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- Authors
- Lenoir, M., Starosciak, A. K., Ledon, J., Booth, C., Zakharova, E., Wade, D., Vignoli, B., & Izenwasser, S.
- Affiliations
- University of Miami (US)
- Corresponding author
- Izenwasser, Sari
- Venue
- Pharmacology Biochemistry and Behavior
- Publisher
- Elsevier BV
- Published
- 2015-05
- Volume
- 132
- Pages
- 56-62
- ISSN
- 0091-3057 (ISSN-L)
- PMC
- PMC4552616
- OpenAlex
- W1983987663
- Cited by
- 40
- References
- 63
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 5 · 2022: 2 · 2021: 4 · 2020: 3 · 2019: 4 · 2018: 3 · 2017: 4 · 2016: 6 · 2015: 4
- FWCI
- 4.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Pharmacology Biochemistry and Behavior (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Iris (University of Trento) (submittedVersion, cc-by-nc-nd)
- HAL (submittedVersion)
- Funders
- National Institute on Drug Abuse
- NIH Office of Research on Women's Health (DA 024584-0002)
- 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
- sex differences, nicotine reward, conditioned place preference, nucleus accumbens, caudate-putamen, smoking cessation, tobacco dependence
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