Glutamate transporter 1-mediated antidepressant-like effect in a rat model of chronic unpredictable stress.
10.1007/s11596-014-1362-5
- Author:
Jian-xin CHEN
1
;
Li-hua YAO
;
Bi-bo XU
;
Kun QIAN
;
Hui-ling WANG
;
Zhong-chun LIU
;
Xiao-ping WANG
;
Gao-hua WANG
Author Information
1. Department of Psychiatry, Renmin Hospital, Wuhan University, Wuhan, 430060, China, CHY_990802@163.com.
- Publication Type:Journal Article
- MeSH:
Animals;
Antidepressive Agents, Second-Generation;
pharmacology;
Behavior, Animal;
drug effects;
Brain;
metabolism;
pathology;
Chronic Disease;
Depressive Disorder, Major;
drug therapy;
metabolism;
pathology;
Excitatory Amino Acid Transporter 2;
metabolism;
Fluoxetine;
pharmacology;
Humans;
Male;
Rats;
Rats, Sprague-Dawley;
Stress, Psychological;
drug therapy;
metabolism;
pathology
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2014;34(6):838-844
- CountryChina
- Language:English
-
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.
