Nicotine exposure in adolescence alters the response of serotonin systems to nicotine administered subsequently in adulthood
Abstract
Developmental nicotine exposure produces lasting changes in serotonin (5-HT) function. We gave nicotine to adolescent rats (postnatal days, PD, 30-47), simulating plasma levels in smokers, and then examined the subsequent effects of nicotine given again in young adulthood (PD 90-107), focusing on 5-HT(1A) and 5-HT(2) receptors and the 5-HT transporter during nicotine treatment (PD 105) and withdrawal (PD 110, 120, 130), and long-term changes (PD 180). Adolescent nicotine exposure by itself evoked long-term elevations in cerebrocortical binding parameters in males that emerged in young adulthood. Nicotine given in adulthood produced transient elevations in 5-HT receptor expression in both males and females during withdrawal, and persistent upregulation in the male cerebral cortex. In contrast, females showed decrements in cerebrocortical 5-HT receptors by PD 180. Adolescent nicotine exposure altered the responses to nicotine given in adulthood, sensitizing the initial effects and changing both the withdrawal response and long-term actions. Our results thus provide mechanistic evidence that nicotine exposure, during the period in which nearly all smokers begin to use tobacco, reprograms the future response of 5-HT systems to nicotine.
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Serotonin systems are uniquely sensitive to nicotine during adolescence.
“Serotonin systems are also uniquely sensitive to nicotine during adolescence (Slotkin & Seidler, 2009; Bang & Commons, 2011; Dao et al., 2011).”
From Unique, long-term effects of nicotine on adolescent brain. (2020) · cites this paper as Slotkin & Seidler, 2009
Cites
Slotkin, T. A. (2004) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2003.06.001 · Cited by 544 · see citing works
Self-citationAre adolescent smokers dependent on nicotine? A review of the evidence
Colby, S. M., Tiffany, S. T., Shiffman, S., & Niaura, R. S. (2000) · Drug and Alcohol Dependence · doi:10.1016/s0376-8716(99)00166-0 · Cited by 312 · see citing works
Diminished nicotine withdrawal in adolescent rats: implications for vulnerability to addiction
O’Dell, L. E., Bruijnzeel, A. W., Smith, R. T., Parsons, L. H., Merves, M. L., Goldberger, B. A., Richardson, H. N., Koob, G. F., & Markou, A. (2006) · Psychopharmacology · doi:10.1007/s00213-006-0383-6 · Cited by 153 · see citing works
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<scp>N</scp> icotine and the adolescent brain
Yuan, M., Cross, S. J., Loughlin, S. E., & Leslie, F. M. (2015) · The Journal of Physiology · doi:10.1113/jp270492 · Cited by 582 · see citing works
Unique, 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
Adolescent nicotine induces persisting changes in development of neural connectivity.
Smith, R. F., McDonald, C. G., Bergstrom, H. C., Ehlinger, D. G., & Brielmaier, J. M. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.05.019 · Cited by 120 · see citing works
- Authors
- Slotkin, T. A., & Seidler, F. J.
- Affiliations
- Duke University (US)
- ORCID
- Slotkin, Theodore A.
- Venue
- Developmental Neuroscience
- Publisher
- S. Karger AG
- Published
- 2009
- Volume
- 31
- Issue
- 1-2
- Pages
- 58-70
- ISSN
- 0378-5866 (ISSN-L)
- 1421-9859
- OpenAlex
- W2055422934
- Cited by
- 22
- References
- 3
- Citations by year
- 2025: 4 · 2024: 1 · 2022: 1 · 2020: 2 · 2019: 2 · 2017: 1 · 2016: 3 · 2015: 3 · 2014: 1
- FWCI
- 0.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Developmental Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- 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
- adolescent nicotine exposure, serotonergic system, 5-HT1A receptor, 5-HT2 receptor, serotonin transporter, nicotine withdrawal, nicotine sensitization, sex differences, cerebral cortex, tobacco initiation
- MeSH terms
- Affect, Aging, Animals, Brain Stem, Data Interpretation, Statistical, Female, Male, Neurons, Nicotine, Serotonin, Substance Withdrawal Syndrome, Rats, Sprague-Dawley, Nicotinic Agonists, Receptor, Serotonin, 5-HT1A, Receptors, Serotonin, 5-HT2, Serotonin Plasma Membrane Transport Proteins, Rats
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