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中缝中核5-羟色胺能神经元调控焦虑和抑郁样行为 

李双, 姚文青, 陶冶铮, 马兰, 刘星^*

复旦大学基础医学院药理研究中心，上海 200032

摘要

中枢神经递质中，5-羟色胺(5-hydroxtryptamine, 5-HT)作用广泛，对情绪调节、感觉传输和认知行为等都有重要调节作用。5-HT能神经元数量较少，主要分布于脑干中线的中缝背核(dorsal raphe nucleus, DR)和中缝中核(median raphe nucleus, MR)。之前的研究主要聚焦于DR核团的功能，对MR核团5-HT能神经元的功能知之甚少。本研究以Pet1-Cre转基因小鼠作为研究对象，通过DREADDs技术特异性操控MR核团5-HT能神经元的活动，进而观察MR核团5-HT能神经元在焦虑和抑郁样行为中的作用。结果显示，在旷场实验与高架十字迷宫实验中，抑制小鼠MR核团5-HT能神经元能减轻小鼠焦虑样行为。在蔗糖偏爱实验和强迫游泳实验中，抑制小鼠MR核团5-HT能神经元能减轻小鼠抑郁样行为，激活MR核团5-HT能神经元则增强小鼠的抑郁样行为。这些结果提示MR核团5-HT能神经元在调节焦虑和抑郁样行为中发挥关键性作用。

关键词： 5-羟色胺; 中缝中核; 焦虑; 抑郁

分类号：R964

Serotonergic neurons in the median raphe nucleus mediate anxiety- and depression- like behavior

LI Shuang, YAO Wen-Qing, TAO Ye-Zheng, Ma Lan, LIU Xing^*

The Pharmacology Research Center, Shanghai Medical College, Fudan University, Shanghai 200032, China

Abstract

Serotonin (5-hydroxtryptamine, 5-HT), one of the central neurotransmitters, is the most important modulator for emotion regulation, sensory processing, cognitive control, etc. The serotonergic neurons are limited in amount and mainly distributed in the dorsal raphe nucleus (DR) and the median raphe nucleus (MR) in the midline of the brain stem. Previous studies mainly focused on the function of 5-HT neurons in the DR, but little is known about 5-HT neurons in MR. In the present study, with Pet1-Cre transgenic mice and DREADDs technology, we specifically activated or silenced 5-HT neurons in the MR, and aimed to explore their roles in anxiety- and depressive-like behaviors. The results showed that silencing 5-HT neurons in the MR decreased anxiety-like behaviors in the open field and elevated plus maze tasks. Inhibition of 5-HT neurons in the MR decreased depressive-like behaviors in the sucrose preference and forced swim test, while activation of 5-HT neurons in the MR enhanced depressive-like behaviors in the sucrose preference test. These results suggest that the 5-HT neurons in the MR play a key role in regulating anxiety- and depression-like behaviors.

Key words: Serotonin; median raphe nucleus; system anxiety; depression

收稿日期：2018-03-05　　录用日期：2018-05-22

通讯作者：刘星　　E-mail: xingliu@fudan.edu.cn

DOI: 10.13294/j.aps.2018.0044

引用本文：

李双, 姚文青, 陶冶铮, 马兰, 刘星. 中缝中核5-羟色胺能神经元调控焦虑和抑郁样行为 [J]. 生理学报 2018; 70 (3): 228-236.

LI Shuang, YAO Wen-Qing, TAO Ye-Zheng, Ma Lan, LIU Xing. Serotonergic neurons in the median raphe nucleus mediate anxiety- and depression- like behavior. Acta Physiol Sin 2018; 70 (3): 228-236 (in Chinese with English abstract).