Impact of acute nicotine exposure on monoaminergic systems in adolescent and adult male and female rats
Abstract
Adolescence is a period of risk for beginning tobacco addiction. Differential neural response to nicotine in adolescents vs. adults may help explain the increased vulnerability to nicotine self-administration seen with adolescent onset. We indexed the effects of acute nicotine ditartrate (0.4 mg/kg, salt weight) administration on dopamine (DA) and serotonin (5HT) as well as the DA metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in several brain regions (nucleus accumbens, striatum and frontal cortex) of 6-week old (adolescent) and 10-week old (young adult) Sprague-Dawley rats. When nicotine was administered DA concentrations in the accumbens were significantly higher in adults than in adolescents, whereas there was no age-related difference without nicotine. However neither age group showed a significant effect of nicotine vs. age-matched controls. DA turnover in the accumbens was significantly greater in adolescent females in response to nicotine, but adult females did not show this effect and neither did males of either age group. DA turnover in the striatum was significantly higher in adolescents than adults regardless of nicotine administration. In the frontal cortex, there was a more complex effect. Without nicotine, adult male rats had higher DA concentrations than adolescent males, whereas female rats did not differ from adolescent to adult ages. When given nicotine, the age effect was no longer seen in males. However, there was not a significant effect of nicotine vs. age-matched controls in either age group. No age or nicotine effects were seen in females. 5HT in the accumbens was significantly increased by nicotine administration in adults but not in adolescents. Altered neural responsivity of adolescents to nicotine-induced neural effects particularly in accumbens DA and 5HT may be related to the increased nicotine dose concentrations they self-administer.
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Adolescent rodents show greater DA release in the NAc in response to acute nicotine compared to adult counterparts, despite similar baseline measures.
“Adolescent rodents show greater DA release in the NAc in response to acute nicotine when compared to adult counterparts, despite similar baseline measures [85, 86].”
From Adolescent nicotine exposure and persistent neurocircuitry changes: unveiling lifelong psychiatric risks (2025) · cites this paper as [86]
Cites
The adolescent brain and age-related behavioral manifestations
Spear, L. P. (2000) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(00)00014-2 · Cited by 5,433 · see citing works
A stereotaxic atlas of the rat brain
Brodal, P. (1980) · Neuroscience · doi:10.1016/0306-4522(80)90013-5 · Cited by 2,799 · see citing works
Competitiveness, risk taking, and violence: the young male syndrome
WILSON, M. I., & Daly, M. (1985) · Ethology and Sociobiology · doi:10.1016/0162-3095(85)90041-x · Cited by 1,242 · see citing works
Becker, J. B., & Hu, M. (2008) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2007.07.003 · Cited by 1,003 · see citing works
Weiss, F., Lorang, M. T., Bloom, F. E., & Koob, G. F. (1993) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)39420-6 · Cited by 751 · see citing works
Preventing Tobacco Use Among Young People: A Report of the Surgeon General
(1994) · PsycEXTRA Dataset · doi:10.1037/e601082007-001 · Cited by 690 · see citing works
Neurocircuitry Targets in Ethanol Reward and Dependence
Koob, G. F., Roberts, A. J., Schulteis, G., Parsons, L. H., Heyser, C. J., Hyytiä, P., Merlo‐Pich, E., & Weiss, F. (1998) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1998.tb03611.x · Cited by 560 · see citing works
Periadolescence: age-dependent behavior and psychopharmacological responsivity in rats
Spear, L. P., & Brake, S. C. (1983) · Developmental Psychobiology · doi:10.1002/dev.420160203 · Cited by 539 · see citing works
Serotonin, dopamine and GABA involvement in alcohol drinking of selectively bred rats
McBride, W. J., Murphy, J. M., Lumeng, L., & Li, T. (1990) · Alcohol · doi:10.1016/0741-8329(90)90005-w · Cited by 297 · see citing works
Ethanol preferentially stimulates dopamine release in the nucleus accumbens of freely moving rats
Chiara, G. D., & Impérato, A. (1985) · European Journal of Pharmacology · doi:10.1016/0014-2999(85)90598-9 · Cited by 287 · see citing works
Nicotine and the adolescent brain: insights from an animal model
Slotkin, T. (2002) · Neurotoxicology and Teratology · doi:10.1016/s0892-0362(02)00199-x · Cited by 284 · see citing works
Age-dependent effects of nicotine on locomotor activity and conditioned place preference in rats
Belluzzi, J., Lee, A., Oliff, H., & Leslie, F. (2004) · Psychopharmacology · doi:10.1007/s00213-003-1758-6 · Cited by 280 · see citing works
Initiation of Cigarette Smoking and Subsequent Smoking Behavior among U.S. High School Students
Everett, S. A., Warren, C. W., Sharp, D. J., Kann, L. K., Husten, C. G., & Crossett, L. S. (1999) · Preventive Medicine · doi:10.1006/pmed.1999.0560 · Cited by 274 · see citing works
How long will today's new adolescent smoker be addicted to cigarettes?
Pierce, J. P., & Gilpin, E. A. (1996) · American Journal of Public Health · doi:10.2105/ajph.86.2.253 · Cited by 273 · see citing works
Evidence for enhanced neurobehavioral vulnerability to nicotine during periadolescence in rats
Adriani, W., Spijker, S., Deroche-Gamonet, V., Laviola, G., Le Moal, M., Smit, A. B., & Piazza, P. V. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-11-04712.2003 · Cited by 257 · see citing works
Nicotine-induced conditioned place preference in adolescent and adult rats
Vastola, B. J., Douglas, L. A., Varlinskaya, E. I., & Spear, L. P. (2002) · Physiology & Behavior · doi:10.1016/s0031-9384(02)00818-1 · Cited by 251 · see citing works
Acetaldehyde Enhances Acquisition of Nicotine Self-Administration in Adolescent Rats
Belluzzi, J. D., Wang, R., & Leslie, F. M. (2004) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300586 · Cited by 245 · see citing works
Eddins, D. M., Cerutti, D. T., Williams, P., Linney, E. A., & Levin, E. D. (2009) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2009.02.005 · Cited by 237 · see citing works
Self-citationTrauth, J. A., Seidler, F. J., McCook, E. C., & Slotkin, T. A. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01994-0 · Cited by 230 · see citing works
Adolescent-onset nicotine self-administration modeled in female rats
Levin, E. D., Rezvani, A. H., Montoya, D., Rose, J. E., & Swartzwelder, H. S. (2003) · Psychopharmacology · doi:10.1007/s00213-003-1486-y · Cited by 218 · see citing works
Self-citationDevelopmentally Moderated Expressions of the Neuropathology Underlying Schizophrenia
Walker, E. F. (1994) · Schizophrenia Bulletin · doi:10.1093/schbul/20.3.453 · Cited by 216 · see citing works
Are adolescents more vulnerable to drug addiction than adults? Evidence from animal models
Schramm-Sapyta, N. L., Walker, Q. D., Caster, J. M., Levin, E. D., & Kuhn, C. M. (2009) · Psychopharmacology · doi:10.1007/s00213-009-1585-5 · Cited by 215 · see citing works
Self-citationTrends in cigarette smoking among US adolescents, 1974 through 1991.
Nelson, D. E., Giovino, G. A., Shopland, D. R., Mowery, P., Mills, S. L., & Eriksen, M. P. (1995) · American Journal of Public Health · doi:10.2105/ajph.85.1.34 · Cited by 209 · see citing works
Shram, M. J., Funk, D., Li, Z., & Lê, A. D. (2006) · Psychopharmacology · doi:10.1007/s00213-006-0373-8 · Cited by 192 · see citing works
Trauth, J. A., Seidler, F. J., & Slotkin, T. A. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02208-3 · Cited by 189 · see citing works
Fetal and adolescent nicotine administration: effects on CNS serotonergic systems
Xu, Z., Seidler, F. J., Ali, S. F., Slikker, W., & Slotkin, T. A. (2001) · Brain Research · doi:10.1016/s0006-8993(01)02797-4 · Cited by 186 · see citing works
Emergence of sex differences in the development of substance use and abuse during adolescence
Kuhn, C. M. (2015) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2015.06.003 · Cited by 182 · see citing works
Initial tobacco use episodes in children and adolescents: current knowledge, future directions
Eissenberg, T., & Balster, R. L. (2000) · Drug and Alcohol Dependence · doi:10.1016/s0376-8716(99)00164-7 · Cited by 170 · 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
Abreu-Villaça, Y., Seidler, F. J., Qiao, D., Tate, C. A., Cousins, M. M., Thillai, I., & Slotkin, T. A. (2003) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300221 · Cited by 151 · see citing works
Trauth, J. A., Seidler, F. J., Ali, S. F., & Slotkin, T. A. (2001) · Brain Research · doi:10.1016/s0006-8993(00)03227-3 · Cited by 150 · see citing works
Levin, E. D., Lawrence, S. S., Petro, A., Horton, K., Rezvani, A. H., Seidler, F. J., & Slotkin, T. A. (2007) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2007.02.002 · Cited by 147 · see citing works
Self-citationDevelopmental regulation of nicotinic acetylcholine receptors within midbrain dopamine neurons
Azam, L., Chen, Y., & Leslie, F. M. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2006.11.011 · Cited by 138 · see citing works
Doura, M. B., Gold, A. B., Keller, A. B., & Perry, D. C. (2008) · Brain Research · doi:10.1016/j.brainres.2008.03.056 · Cited by 129 · see citing works
Abreu‐Villaça, Y., Seidler, F. J., Tate, C. A., & Slotkin, T. A. (2003) · Brain Research · doi:10.1016/s0006-8993(03)02885-3 · Cited by 120 · see citing works
Acquisition of nicotine self-administration in adolescent rats given prolonged access to the drug
Chen, H., Matta, S. G., & Sharp, B. M. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301135 · Cited by 112 · see citing works
Ed, L., Kaplan, S., & Boardman, A. (1997) · PubMed · Cited by 110 · see citing works
Nicotine effects on learning in zebrafish: the role of dopaminergic systems
Eddins, D. M., Petro, A. E., Williams, P., Cerutti, D. T., & Levin, E. D. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1287-4 · Cited by 103 · see citing works
Self-citationAdolescent and adult female rats differ in sensitivity to nicotine's activity effects
ELLIOTT, B., Faraday, M. M., PHILLIPS, J., & Grunberg, N. E. (2005) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2005.01.019 · Cited by 102 · see citing works
Klein, L. C., Stine, M. M., Vandenbergh, D. J., Whetzel, C. A., & Kamens, H. M. (2004) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2004.01.005 · Cited by 95 · see citing works
Adolescent Vulnerabilities to Chronic Alcohol or Nicotine Exposure: Findings From Rodent Models
Barron, S., White, A., Swartzwelder, H. S., Bell, R. L., Rodd, Z. A., Slawecki, C. J., Ehlers, C. L., Levin, E. D., Rezvani, A. H., & Spear, L. P. (2005) · Alcoholism: Clinical and Experimental Research · doi:10.1097/01.alc.0000179220.79356.e5 · Cited by 90 · see citing works
Self-citationNicotine Withdrawal in Adolescent and Adult Rats
O’Dell, L. E., Bruijnzeel, A. W., Ghozland, S. G., Markou, A., & Koob, G. F. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1308.022 · Cited by 90 · see citing works
Cheeta, S. (2001) · Neuropsychopharmacology · doi:10.1016/s0893-133x(01)00258-5 · Cited by 84 · see citing works
O’Dell, L. E., Torres, O. V., Natividad, L. A., & Tejeda, H. A. (2006) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2006.11.003 · Cited by 84 · see citing works
A psychobiological framework of the substrates that mediate nicotine use during adolescence
O'Dell, L. E. (2009) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.07.039 · Cited by 81 · see citing works
Increased nicotine self-administration following prenatal exposure in female rats
LEVIN, E., LAWRENCE, S., PETRO, A., HORTON, K., SEIDLER, F., & SLOTKIN, T. (2006) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2006.11.006 · Cited by 80 · see citing works
Self-citationAdolescent and adult rats' aversion to flavors previously paired with nicotine
WILMOUTH, C. E., & SPEAR, L. P. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1308.065 · Cited by 80 · see citing works
Age-dependent differences in nicotine reward and withdrawal in female mice
Kota, D., Martin, B. R., & Damaj, M. I. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1117-8 · Cited by 72 · see citing works
Collins, S. L., Montano, R. E., & Izenwasser, S. (2004) · Developmental Brain Research · doi:10.1016/j.devbrainres.2004.08.004 · Cited by 71 · see citing works
Kane, V. B., Fu, Y., Matta, S. G., & Sharp, B. M. (2004) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.059899 · Cited by 66 · see citing works
Pharmacogenetic models of alcoholism.
Li, T.-K., & McBride, W. J. H. (1995) · PubMed · Cited by 65 · see citing works
Sonntag, K. C., Brenhouse, H. C., Freund, N., Thompson, B. S., Puhl, M., & Andersen, S. L. (2014) · Psychopharmacology · doi:10.1007/s00213-013-3399-8 · Cited by 64 · see citing works
Neurochemical alterations produced by daily nicotine exposure in periadolescent vs. adult male rats
Collins, S. L., Wade, D., Ledon, J., & Izenwasser, S. (2004) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2004.08.039 · Cited by 62 · see citing works
Craig, E. L., Zhao, B., Cui, J. Z., Novalen, M., Miksys, S., & Tyndale, R. F. (2014) · Drug Metabolism and Disposition · doi:10.1124/dmd.114.058719 · Cited by 59 · see citing works
Nicotine-induced monoamine neurotransmitter changes in the brain of young rats
Shearman, E., Fallon, S., Sershen, H., & Lajtha, A. (2008) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2008.03.017 · Cited by 55 · see citing works
Abreu-Villaça, Y., Seidler, F. J., & Slotkin, T. A. (2003) · Brain Research · doi:10.1016/s0006-8993(03)03368-7 · Cited by 55 · see citing works
Rezvani, A. H., & Levin, E. D. (2004) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2004.03.007 · Cited by 51 · see citing works
Self-citationNatividad, L. A., Torres, O. V., Friedman, T. C., & O’Dell, L. E. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.10.003 · Cited by 45 · see citing works
Threshold of adulthood for the onset of nicotine self-administration in male and female rats
Levin, E. D., Slade, S. K., Wells, C., Cauley, M. C., Petro, A. E., Vendittelli, A., Johnson, M. L., Williams, P., Horton, K., & Rezvani, A. H. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.08.005 · Cited by 45 · see citing works
Self-citationRole of insular cortex D1 and D2 dopamine receptors in nicotine self-administration in rats
Kutlu, M. G., Burke, D., Slade, S., Hall, B. J., Rose, J. E., & Levin, E. D. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.08.005 · Cited by 41 · see citing works
Self-citationSlotkin, T. A., Cousins, M. M., & Seidler, F. J. (2004) · Brain Research · doi:10.1016/j.brainres.2004.10.009 · Cited by 40 · see citing works
Nicotine causes age-dependent changes in gene expression in the adolescent female rat brain
Polesskaya, O. O., Fryxell, K. J., Merchant, A. D., Locklear, L. L., Ker, K.-F., McDonald, C. G., Eppolito, A. K., Smith, L. N., Wheeler, T. L., & Smith, R. F. (2007) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2006.11.005 · Cited by 36 · see citing works
Slotkin, T. A., & Seidler, F. J. (2006) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2006.06.001 · Cited by 33 · see citing works
Ketanserin attenuates nicotine-induced working memory improvement in rats
Levin, E. D., Icenogle, L., & Farzad, A. (2005) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2005.08.017 · Cited by 31 · see citing works
Self-citationLevin, E. D. (1997) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(97)00052-x · Cited by 30 · see citing works
Self-citationDifferences in Age of Smoking Initiation Between Blacks and Whites—United States
(1991) · JAMA · doi:10.1001/jama.1991.03470220028008 · Cited by 30 · see citing works
Badanich, K. A., & Kirstein, C. L. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1308.054 · Cited by 25 · see citing works
Neuro-anatomic mapping of dopamine D1 receptor involvement in nicotine self-administration in rats
Hall, B. J., Slade, S. K., Allenby, C. E., Kutlu, M. G., & Levin, E. D. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.03.005 · Cited by 24 · see citing works
Self-citationAdolescent reward system perseveration due to nicotine: Studies with methylphenidate
Nolley, E. P., & Kelley, B. M. (2007) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2006.09.026 · Cited by 24 · see citing works
Differential effects of d-amphetamine in mature and immature rats
Bauer, R. H., & Duncan, D. L. (1975) · Physiological Psychology · doi:10.3758/bf03337532 · Cited by 24 · see citing works
Cadoni, C., Muto, T., & Chiara, G. D. (2009) · Neuropharmacology · doi:10.1016/j.neuropharm.2009.07.033 · Cited by 21 · see citing works
Individual differences in responses to nicotine: tracking changes from adolescence to adulthood
Li, M., Mead, A., & Bevins, R. A. (2009) · Acta Pharmacologica Sinica · doi:10.1038/aps.2009.55 · Cited by 18 · see citing works
Interaction of nicotinic and histamine H3 systems in the radial-arm maze repeated acquisition task
Kholdebarin, E., Caldwell, D. P., Blackwelder, W. P., et al. (2007) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.04.051 · Cited by 14 · see citing works
Sex and age differences in approach behavior toward a port that delivers nicotine vapor
Espinoza, V. E., Giner, P., Liano, I., Mendez, I. A., & O’Dell, L. E. (2022) · Journal of the Experimental Analysis of Behavior · doi:10.1002/jeab.756 · Cited by 13 · see citing works
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- Authors
- Eddins, D., Petro, A., & Levin, E. D.
- Affiliations
- Duke Medical Center (US)
- Corresponding author
- Levin, Edward D.
- ORCID
- Levin, Edward D.
- Venue
- Neurotoxicology and Teratology
- Publisher
- Elsevier BV
- Published
- 2022-09
- Volume
- 93
- Pages
- 107122
- ISSN
- 0892-0362 (ISSN-L)
- OpenAlex
- W4295919659
- Cited by
- 2
- References
- 74
- Citations by year
- 2025: 1 · 2024: 1
- FWCI
- 0.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Neurotoxicology and Teratology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Drug Abuse (DA027840, DA015756)
- 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
- monoaminergic systems, dopamine, serotonin, DOPAC, dopamine turnover, nucleus accumbens, striatum, frontal cortex, adolescence, sex differences, age differences
- MeSH terms
- Animals, Dopamine, Female, Male, Nicotine, Nucleus Accumbens, Serotonin, 3,4-Dihydroxyphenylacetic Acid, Rats, Sprague-Dawley, Rats
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