Dopamine in prefrontal cortices is implicated in cognitive and emotional functions, and the dysfunction of prefrontal dopamine has been associated with cognitive and emotional deficits in mental illnesses. These findings have led to clinical trials of dopamine-targeting drugs and brain imaging of dopamine receptors in patients with mental illnesses. Rodent studies have suggested that dopaminergic pathway projecting to the medial prefrontal cortex (mPFC) suppresses stress susceptibility. Although various types of mPFC neurons express several dopamine receptor subtypes, previous studies neither isolated a role of dopamine receptor subtype nor identified the site of its action in mPFC. Using social defeat stress (SDS) in mice, here we identified a role of dopamine D1 receptor subtype in mPFC excitatory neurons in suppressing stress susceptibility. Repeated social defeat stress (R-SDS) reduces the expression of D1 receptor subtype in mPFC of mice susceptible to R-SDS. Knockdown of D1 receptor subtype in whole neuronal populations or excitatory neurons in mPFC facilitates the induction of social avoidance by SDS. Single social defeat stress (S-SDS) induces D1 receptor-mediated extracellular signal-regulated kinase phosphorylation and c-Fos expression in mPFC neurons. Whereas R-SDS reduces dendritic lengths of mPFC layer II/III pyramidal neurons, S-SDS increases arborization and spines of apical dendrites of these neurons in a D1 receptor-dependent manner. Collectively, our findings show that D1 receptor subtype and related signaling in mPFC excitatory neurons mediate acute stress-induced dendritic growth of these neurons and contribute to suppression of stress susceptibility. Therefore, we propose that D1 receptor-mediated dendritic growth in mPFC excitatory neurons suppresses stress susceptibility.

中文翻译：

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多巴胺D1受体亚型介导前额内侧皮层的兴奋性神经元中的急性应激诱导的树突状生长，并有助于抑制小鼠的应激敏感性。

前额叶皮层中的多巴胺与认知和情感功能有关，而额叶前多巴胺的功能障碍与精神疾病的认知和情感缺陷有关。这些发现导致了针对精神疾病患者的多巴胺靶向药物的临床试验和多巴胺受体的脑成像。啮齿动物研究表明，投射到内侧前额叶皮层（mPFC）的多巴胺能途径可抑制应激敏感性。尽管各种类型的mPFC神经元表达几种多巴胺受体亚型，但先前的研究既未分离出多巴胺受体亚型的作用，也未确定其在mPFC中的作用位点。在小鼠中使用社交挫败应激（SDS），我们在mPFC兴奋性神经元中确定了多巴胺D1受体亚型在抑制应激易感性中的作用。反复的社交挫败压力（R-SDS）降低了对R-SDS易感的小鼠mPFC中D1受体亚型的表达。敲除整个mPFC中的整个神经元群体或兴奋性神经元中的D1受体亚型有助于通过SDS诱导社会回避。单一的社交挫败压力（S-SDS）在mPFC神经元中诱导D1受体介导的细胞外信号调节激酶磷酸化和c-Fos表达。R-SDS减少了mPFC层II / III锥体神经元的树突长度，而S-SDS以D1受体依赖性方式增加了这些神经元的树突和根尖树突。总的来说，我们的发现表明，mPFC兴奋性神经元中的D1受体亚型和相关信号介导了这些神经元的急性应激诱导的树突状生长，并有助于抑制应激敏感性。所以，