Epidemiological studies report strong association between mood disorders and tobacco addiction. This high comorbidity requires adequate treatment but the underlying mechanisms are unknown. We demonstrate that nicotine exposure, independent of drug withdrawal effects, increases stress sensitivity, a major risk factor in mood disorders. Nicotine and stress concur to induce long-lasting cellular adaptations within the dopamine (DA) system. This interplay is underpinned by marked remodeling of nicotinic systems, causing increased ventral tegmental area (VTA) DA neurons' activity and stress-related behaviors, such as social aversion. Blocking β2 or α7 nicotinic acetylcholine receptors (nAChRs) prevents, respectively, the development and the expression of social stress-induced neuroadaptations; conversely, facilitating α7 nAChRs activation specifically in the VTA promotes stress-induced cellular and behavioral maladaptations. Our work unravels a complex nicotine-stress bidirectional interplay and identifies α7 nAChRs as a promising therapeutic target for stress-related psychiatric disorders.

中文翻译：

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烟碱受体通过多巴胺细胞的活性介导应激烟碱的有害相互作用。

流行病学研究报告说，情绪障碍与烟草成瘾之间有很强的联系。这种高合并症需要适当的治疗，但潜在的机制尚不清楚。我们证明，烟碱暴露与药物戒断作用无关，可增加压力敏感性，这是情绪障碍的主要危险因素。尼古丁和压力共同导致多巴胺（DA）系统内持久的细胞适应。烟碱系统的显着重塑支撑了这种相互作用，导致腹侧被盖区（VTA）DA神经元的活动增加以及与压力相关的行为，例如社交厌恶。阻断β2或α7烟碱乙酰胆碱受体（nAChRs）分别阻止社交应激诱导的神经适应的发展和表达。反过来，专门在VTA中促进α7nAChRs活化会促进应激诱导的细胞和行为适应不良。我们的工作揭示了复杂的尼古丁-压力双向相互作用，并将α7nAChRs确定为与压力相关的精神疾病的有希望的治疗靶标。