Long-term effects of adolescent versus adult nicotine self-administration on cholinergic modulation of dopamine in the nucleus accumbens core.

Adolescence is a developmental period marked by significant alterations to brain neurobiology and behavior. Adolescent nicotine use disrupts developmental trajectories and increases vulnerability to maladaptive drug-taking in adulthood. The mesolimbic dopamine (DA) system, including the nucleus accumbens core (NAc), mediates the reinforcing effects of nicotine. While dopaminergic reorganization is necessary for the transition into adulthood, how adolescent nicotine exposure affects cholinergic modulation of adult NAc DA dynamics is less understood. Here, we use 12 days of intravenous self-administration (SA) and ex vivo fast-scan cyclic voltammetry (FSCV) to explore the effects of adolescent (P31-42) versus adult (P63-75) nicotine (0.03mg/kg/infusion) intake on DA dynamics following three weeks of forced abstinence in adult male rats. This three-week abstinence period ensured that all neurochemical measurements were performed in adulthood. Consistent with the literature, we show that adolescent and adult male rats self-administer similar amounts of nicotine. While adult nicotine exposure + forced abstinence decreased NAc DA release relative to adult saline exposure, we found no difference in adult NAc DA release after adolescent nicotine or saline exposure. Investigating α6-versus non-α6-containing nicotinic acetylcholine receptors (nAChRs) revealed differential modulatory effects in adults and adolescents self-administering nicotine relative to respective saline controls. Both α6- and non-α6β2-containing nAChRs facilitation of NAc DA release was increased across frequencies only after adolescent nicotine versus saline SA. These data provide a foundation for understanding the long-term effects of nicotine in adolescence on cholinergic modulation of NAc DA dynamics in adulthood.