Glutamate Transporter 1-mediated Antidepressant-like Effect in a Rat Model of Chronic Unpredictable Stress

作     者：陈建新 姚丽华 徐碧波 钱坤 王惠玲 刘忠纯 王晓萍 王高华 

作者机构：Department of Psychiatry Renmin Hospital Wuhan University Department of Psychology Faculty of Education Hubei University Department of Obstetrics and Gynecology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology 

出 版 物：《Journal of Huazhong University of Science and Technology(Medical Sciences)》 (华中科技大学学报（医学英德文版）)

年 卷 期：2014年第34卷第6期

页      面：838-844页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 100205[医学-精神病与精神卫生学] 10[医学] 

基　　金：supported by the Key Technology Research of Major Mental Illness Prevention and Treatment for the Barriers to the Recognition and Prevention of Depression and Anxiety in the General Hospital China(No.2012BAI01B05) 

主　　题：chronic unpredictable stress glutamate transporter 1 glutamate fluoxetine hippocampus 

摘      要：In recent years, more attention has been paid to the role of the glutamate transporter 1 （GLT-1, EAAT2） in major depressive disorder （MDD）. However, experimental data on brain GLT-1 levels are, to some extent, inconsistent in human postmortem and animal studies, These discrepancies imply that the role of GLT-1 in the pathophysiology of MDD and the action of antidepressants remain obscure. This work was designed to study the impact of chronic unpredictable stress （CUS） for 2 ses- sions per day for 35 days and four weeks of fluoxetine （FLX） on depressive-like behaviors in rats, as well as the concomitant expression of the GLT-1 protein in the hippocampus. Behavioral changes were assessed by the sucrose preference and open field tests. GLT-1 levels were detected by immunohisto- chemistry and Western blot analysis. Our study demonstrated that the animals exposed to CUS showed depressive-like behaviors and exhibited a significant decrease in GLT-1 expression in the hippocampus. Chronic FLX treatment reversed the behavioral deficits and the CUS-induced decrease in GLT-1 levels. Taken together, our results support the reduction of GLT-1 in human postmortem studies in MDD and suggest that GLT-1 may be involved in the antidepressant activity of FLX. Our studies further support the notion that GLT-1 is an attractive candidate molecule associated with the fundamental processes of MDD and may be a potential, and novel pharmacological target for the treatment of MDD.