Iacino Melody C, Pitts Elizabeth G, Bonsib Amelia G, Sexton Lacey L, Ferris Mark J
Department of Translational Neuroscience, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Department of Translational Neuroscience, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Drug Alcohol Depend. 2025 Mar 1;268:112555. doi: 10.1016/j.drugalcdep.2025.112555. Epub 2025 Jan 15.
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.
青春期是一个大脑神经生物学和行为发生重大变化的发育时期。青少年使用尼古丁会扰乱发育轨迹，并增加成年后出现适应不良药物使用行为的易感性。中脑边缘多巴胺（DA）系统，包括伏隔核核心（NAc），介导尼古丁的强化作用。虽然多巴胺能重组对于向成年期的过渡是必要的，但青少年尼古丁暴露如何影响成年NAc DA动态的胆碱能调节却鲜为人知。在这里，我们使用12天的静脉自我给药（SA）和离体快速扫描循环伏安法（FSCV），来探究青少年（P31 - 42）与成年（P63 - 75）雄性大鼠在摄入尼古丁（0.03mg/kg/输注）后，经过三周强制戒断，对成年雄性大鼠DA动态的影响。这三周的戒断期确保了所有神经化学测量都是在成年期进行的。与文献一致，我们发现青少年和成年雄性大鼠自我给药的尼古丁量相似。虽然成年期尼古丁暴露 + 强制戒断相对于成年期生理盐水暴露降低了NAc DA释放，但我们发现青少年尼古丁或生理盐水暴露后成年NAc DA释放没有差异。研究含α6与不含α6的烟碱型乙酰胆碱受体（nAChRs）发现，与各自的生理盐水对照组相比，成年和青少年自我给药尼古丁后存在不同的调节作用。仅在青少年尼古丁与生理盐水SA后，含α6和含非α6β2的nAChRs对NAc DA释放的促进作用在各频率上均增加。这些数据为理解青春期尼古丁对成年期NAc DA动态胆碱能调节的长期影响提供了基础。
