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Psychiatry"],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Abuse or misuse of tobacco, e-cigarettes, or antidepressants may have serious clinical consequences during adolescence, a sensitive period during brain development when the distinct neurobiology of adolescent serotonin (5-HT) and dopamine (DA) systems create unique behavioral vulnerabilities to drugs of abuse.  <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using a pharmacological approach, we modeled the behavioral and neurochemical effects of subchronic (4-day) nicotine (60\u00b5g\/kg, i.v.) or fluoxetine (1mg\/kg, i.v.) exposure in adolescent and adult male rats. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nicotine and fluoxetine significantly enhance quinpirole-induced locomotor activity and initial cocaine self-administration in adolescents, but not adults. These effects were blocked by serotonin 5-HT<jats:sub>1A<\/jats:sub> receptor antagonists, WAY-100,635 (100 \u00b5g\/kg, i.v.) or S-15535 (300 \u00b5g\/kg, i.v.). Neurochemical and anatomical autoradiographic analysis of 8-OH-DPAT-stimulated [<jats:sup>35<\/jats:sup>S]GTP\u03b3S reveal that prior exposure to nicotine and fluoxetine results in both overlapping and distinct effects on regional 5-HT1A receptor activity. Both fluoxetine and nicotine enhance adolescent 5-HT1A receptor activity in the primary motor cortex (M1), whereas fluoxetine alone targets prefrontal cortical neurocircuitry and nicotine alone targets the amygdala. <\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Given their different pharmacological profiles, comparison between WAY-100,635 and S-15535 indicates that postsynaptic 5-HT<jats:sub>1A<\/jats:sub> receptors mediate the behavioral effects of prior nicotine and fluoxetine exposure. In addition, within the adolescent M1, maladaptive changes in 5-HT signaling and 5-HT<jats:sub>1A<\/jats:sub> activity after nicotine or fluoxetine exposure may potentiate hyper-responsiveness to dopaminergic drugs and prime adolescent vulnerability for future substance abuse.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fpsyt.2024.1380123","type":"journal-article","created":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T13:24:03Z","timestamp":1718198643000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Nicotine and fluoxetine alter adolescent dopamine-mediated behaviors via 5-HT1A receptor activation"],"prefix":"10.3389","volume":"15","author":[{"given":"Menglu","family":"Yuan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frances M.","family":"Leslie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,6,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-010-9157-3","article-title":"Adolescent maturation of cortical dopamine","volume":"18","author":"O\u2019Donnell","year":"2010","journal-title":"Neurotox Res"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bandc.2009.10.013","article-title":"Developmental changes in dopamine neurotransmission in adolescence: behavioral implications and issues in assessment","volume":"72","author":"Wahlstrom","year":"2010","journal-title":"Brain Cognit"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1469","DOI":"10.1113\/JP270492","article-title":"Nicotine and the adolescent brain","volume":"593","author":"Yuan","year":"2015","journal-title":"J Physiol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1001\/archpsyc.62.6.593","article-title":"Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication","volume":"62","author":"Kessler","year":"2005","journal-title":"Arch Gen Psychiatry"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2006.12.001","article-title":"Adolescent cortical development: a critical period of vulnerability for addiction","volume":"86","author":"Crews","year":"2007","journal-title":"Pharmacol Biochem Behav"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6745a5","article-title":"Notes from the field: use of electronic cigarettes and any tobacco product among middle and high school students \u2014 United states, 2011\u20132018","volume":"67","author":"Cullen","year":"2018","journal-title":"MMWR. 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