title: Glutamate transporter 1-mediated antidepressant-like effect in a rat model of chronic unpredictable stress.
abstract: 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 sessions 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 immunohistchemistry 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.
authors.affiliation: Department of Psychiatry, Renmin Hospital, Wuhan University, Wuhan, 430060, China.
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Chen
authors.affiliation: Department of Psychiatry, Renmin Hospital, Wuhan University, Wuhan, 430060, China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Yao
authors.affiliation: Department of Psychology, Faculty of Education, Hubei University, Wuhan, 430062, China.
authors.forename: Bi-Bo
authors.initials: BB
authors.lastname: Xu
authors.affiliation: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Qian
authors.affiliation: Department of Psychiatry, Renmin Hospital, Wuhan University, Wuhan, 430060, China.
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, Renmin Hospital, Wuhan University, Wuhan, 430060, China.
authors.forename: Zhong-Chun
authors.initials: ZC
authors.lastname: Liu
authors.affiliation: Department of Psychiatry, Renmin Hospital, Wuhan University, Wuhan, 430060, China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, Renmin Hospital, Wuhan University, Wuhan, 430060, China. wanggaohuad@tom.com.
authors.forename: Gao-Hua
authors.initials: GH
authors.lastname: Wang
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002908:Chronic Disease; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism*; D005473:Fluoxetine / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D018687:Antidepressive Agents, Second-Generation; D027342:Excitatory Amino Acid Transporter 2; C493395:Slc1a2 protein, rat; D005473:Fluoxetine