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环境应激对雄性大鼠抑郁样行为及皮质酮和褪黑素昼夜节律的影响

袁铭, 刘丽京, 徐凌志, 郭田友, 岳晓东, 李素霞^*

1北京大学中国药物依赖性研究所，北京 100191；2北京大学医学部基础医学院药理系，北京 100191；3深圳大学心理与社会学院，深圳 518060；4香港城市大学应用社会科学系，香港 999077

摘要

：环境应激(environmental stress, ES)是慢性不可预见性轻度应激中的应激成分。慢性不可预见性轻度应激抑郁模型通常用于研究抑郁症的发病机制，也可用于研究昼夜节律系统对抑郁的调节作用。然而，ES在多大程度上能对昼夜节律系统产生直接作用尚待研究。本研究旨在观察ES对大鼠抑郁样行为以及大鼠外周血中皮质酮和褪黑素昼夜节律的影响。大鼠分为对照组、低频率ES组和高频率ES组，通过糖水偏爱测试、旷场测试、体重增加及饮食，观察ES对大鼠抑郁、焦虑样行为的影响，并在24 h内每间隔4 h一次采集大鼠尾静脉血，共7次，采用ELISA检测大鼠外周血中24 h皮质酮和褪黑素节律性变化；选择ZT0一个时间点的血浆，检测调节饮食的胆囊收缩素、神经肽Y及瘦素变化。结果显示，与对照组相比，ES可导致大鼠血清中皮质酮和褪黑素的昼夜节律紊乱、瘦素水平增加、体重增量降低，而未表现出抑郁、焦虑样行为。以上结果提示，ES可引起大鼠皮质酮和褪黑素的昼夜节律紊乱。

关键词： 环境应激; 抑郁; 昼夜节律; 皮质酮; 褪黑素

Effects of environmental stress on the depression-like behaviors and the diurnal rhythm of corticosterone and melatonin in male rats

YUAN Ming, LIU Li-Jing, XU Ling-Zhi, GUO Tian-You, YUE Xiao-Dong, LI Su-Xia^*

1National Institute on Drug Dependence, Peking University, Beijing 100191, China； 2 Department of Pharmacology, School of BasicMedical Science, Peking University Health Science Center, Beijing 100191, China； 3College of Psychology, and Sociology, Shenzhen University, Shenzhen 518060, China； 4Department of Applied Social Sciences, City University of Hong Kong, Hong Kong 999077, China

Abstract

Environmental stress (ES) is commonly used in producing chronic unpredictable mild stress to study pathogenesis of depression, including the regulatory role of circadian system on depression. However, the direct effect of ES on the circadian system
has been rarely explored. The present study was aimed to investigate the effect of ES on depression-like behaviors and diurnal rhythm of plasma hormone/peptide levels in male rats. Rats were allocated into control group (CON group), low frequency ES group (LF group) and high frequency ES group (HF group). Sucrose preference test (SPT), open field test (OFT), weight gain, food and water intake were conducted to assess depression- and anxiety-like behaviors. A total of 7 times of the tail venous blood was collected with an interval of 4 h during 24 h from other rats who subjected to the same procedures of ES but not the behavioral tests. The alterations of diurnal rhythm of peripheral plasma corticosterone (CORT) and melatonin, and changes of the cholecystokinin (CCK), neuropeptide Y and leptin levels at zeitgeber time (ZT) 0 were detected by using enzyme-linked immunosorbent assay (ELISA). We found that ES led to a disturbance of diurnal rhythm of CORT and melatonin in the plasma. Besides, it also increased plasma leptin level and decreased body weight gain, but it did not produce depression- and anxiety-like behaviors compared with those rats in the control group. In short, our findings indicated that the ES could induce a disturbance of diurnal rhythm of plasma CORT and melatonin in male rats.

Key words: environmental stress; depression; diurnal rhythm; corticosterone; melatonin

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通讯作者：李素霞　　E-mail: li313@bjmu.edu.cn

引用本文：

袁铭, 刘丽京, 徐凌志, 郭田友, 岳晓东, 李素霞. 环境应激对雄性大鼠抑郁样行为及皮质酮和褪黑素昼夜节律的影响[J]. 生理学报 2016; 68 (3): 215-223.

YUAN Ming, LIU Li-Jing, XU Ling-Zhi, GUO Tian-You, YUE Xiao-Dong, LI Su-Xia. Effects of environmental stress on the depression-like behaviors and the diurnal rhythm of corticosterone and melatonin in male rats. Acta Physiol Sin 2016; 68 (3): 215-223 (in Chinese with English abstract).