Reynolds Lauren M, Faure Philippe, Barik Jacques
Plasticité du Cerveau CNRS UMR8249, École supérieure de physique et de chimie industrielles de la Ville de Paris (ESPCI Paris), Paris, France.
Neuroscience Paris Seine CNRS UMR 8246 INSERM U1130, Institut de Biologie Paris Seine, Sorbonne Université, Paris, France.
Mol Psychiatry. 2025 Aug 29. doi: 10.1038/s41380-025-03110-0.
Nicotine exposure during adolescence has emerged as a significant risk factor for later psychiatric disease. Notably, adolescence is a critical period for the maturation of acetylcholine and dopamine systems, neuromodulators which tightly regulate cognitive, motivational and emotional behaviors known to contribute to psychiatric vulnerability. This review explores whether long-lasting modifications in these neuromodulatory systems following adolescent nicotine exposure underlie the increased vulnerability to mental health disorders. We discuss evidence that nicotine in adolescence leads to enduring molecular, cellular alterations by perturbing the normal trajectory of cholinergic and dopamine systems, and link these changes with potential adverse behavioral outcomes in adulthood. We propose that persistent alterations in acetylcholine and dopamine signaling caused by adolescent nicotine exposure may contribute to the heightened risk for psychiatric disorders including substance abuse, anxio-depressive disorders, and schizophrenia for which deficits in a large spectrum of motivational domains are highly prevalent. The interaction between nicotine and these developing neurotransmitter systems during adolescence raises important questions about the mechanisms driving these changes. Finally, we discuss limitations in the current research and subsequently identify open questions in the field which will help drive forward research on the psychiatric consequences of adolescent nicotine use. Understanding these maladaptations could pave the way for targeted therapeutic strategies to mitigate the adverse effects of adolescent nicotine exposure on brain development and subsequent psychiatric outcomes.
青少年时期接触尼古丁已成为日后患精神疾病的重要风险因素。值得注意的是，青少年时期是乙酰胆碱和多巴胺系统成熟的关键时期，这些神经调质紧密调节认知、动机和情绪行为，而这些行为已知会导致精神易感性。本综述探讨青少年接触尼古丁后这些神经调节系统的长期改变是否是导致心理健康障碍易感性增加的基础。我们讨论了证据表明青少年时期的尼古丁通过扰乱胆碱能和多巴胺系统的正常轨迹导致持久的分子和细胞改变，并将这些变化与成年期潜在的不良行为结果联系起来。我们提出，青少年接触尼古丁导致的乙酰胆碱和多巴胺信号的持续改变可能导致包括药物滥用、焦虑抑郁障碍和精神分裂症在内的精神疾病风险增加，而这些疾病在广泛的动机领域存在缺陷的情况非常普遍。青少年时期尼古丁与这些发育中的神经递质系统之间的相互作用引发了关于驱动这些变化机制的重要问题。最后，我们讨论了当前研究的局限性，并随后确定了该领域的开放性问题，这将有助于推动青少年使用尼古丁对精神影响的研究。了解这些适应不良情况可为有针对性的治疗策略铺平道路，以减轻青少年接触尼古丁对大脑发育和随后精神结果的不利影响。
