Oxytocin Exerts Antidepressant-like effect by potentiating dopaminergic synaptic transmission in the mPFC
Oxytocin Exerts Antidepressant-like effect by potentiating dopaminergic synaptic transmission in the mPFC
复制标题
催产素通过增强 mPFC 中的多巴胺能突触传递来发挥抗抑郁样作用
DOI：
10.1016/j.neuropharm.2019.107836
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发表时间：
2020-01-01
影响因子：
4.7
通讯作者：
Liu, Zhiqiang
中科院分区：
文献类型：
--
作者：
Li, Qian;Zhang, Bing;Liu, Zhiqiang
催产素（OT）和多巴胺（DA）是大脑中与精神和奖励过程密切相关的两个重要元素。OT控制的DA功能调节对社会奖励、社会认知和情绪相关行为等多种行为有影响。以往的研究表明，内侧前额叶皮层（mPFC）多巴胺能传递减少与抑郁症的病理生理相关。然而，OT和DA的相互作用及其在抗抑郁作用中的作用仍有待进一步探索。本研究通过mPFC局部给药研究了OT的抗抑郁作用，并进一步探讨了其潜在机制，表明OT可以增强多巴胺能突触传递，并依赖于mPFC中OT受体（OTR）的激活。我们的研究结果表明，在初始和社会失败应激（SDS）抑郁动物模型中，mPFC局部给予OT均具有抗抑郁（样）作用。机制研究表明，OT增强DA水平依赖于OTR激活，mPFC DA水平升高可能通过激活mPFC细胞内D1/PKA/DARPP32信号通路进一步增强兴奋性突触传递。因此，我们的研究表明，OTR的激活通过增强多巴胺能突触传递来增强兴奋性突触传递，特别是通过依赖于D1R的激活，在mPFC中，这可能是OT介导的抗抑郁（样）作用的潜在机制。通过特异性激活D1/PKA/DAPRR32信号通路，我们的研究结果可能增强了OT在中枢神经系统奖赏回路中的重要作用。
Oxytocin (OT) and dopamine (DA) are two important elements that are closely related to mental and reward processes in the brain. OT controlled DA functional regulation contributes to various behaviours such as social reward, social cognition and emotion-related behaviours. Previous studies indicated that diminished dopaminergic transmission in the medial prefrontal cortex (mPFC) is correlated with the pathophysiology of depression. However, the interaction of OT and DA and their roles in antidepressant effects still require further exploration. Here, we investigated the antidepressant effect of OT through local mPFC administration, and further explored the underlying mechanisms that indicated that OT could strengthen dopaminergic synaptic transmission with OT receptor (OTR) activation dependent in the mPFC. Our results showed that local administration of OT in the mPFC exerts antidepressant (-like) effects in both naive and social defeat stress (SDS) depressive animal model. Mechanism study suggested that OT enhances DA level with OTR activation dependent, and elevated mPFC DA levels might further enhance excitatory synaptic transmission by activating the D1/PKA/DARPP32 intracellular signalling pathway in the mPFC.Hence, our study revealed that the activation of OTR strengthens excitatory synaptic transmission via the potentiation of dopaminergic synaptic transmission, especially via D1R activation dependent, in the mPFC, which may be the underlying mechanism of antidepressant (-like) effects mediated by OT. With specifically activation of the D1/PKA/DAPRR32 signalling pathway, our results may augment the important role of OT in reward circuits in the central nervous system.