Glutamate transporter 1-mediated antidepressant-like effect in a rat model of chronic unpredictable stress

J Huazhong Univ Sci Technolog Med Sci. 2014 Dec;34(6):838-844. doi: 10.1007/s11596-014-1362-5. Epub 2014 Dec 6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents, Second-Generation / pharmacology*
  • Behavior, Animal / drug effects
  • Brain / metabolism*
  • Brain / pathology
  • Chronic Disease
  • Depressive Disorder, Major / drug therapy
  • Depressive Disorder, Major / metabolism
  • Depressive Disorder, Major / pathology
  • Excitatory Amino Acid Transporter 2 / metabolism*
  • Fluoxetine / pharmacology*
  • Humans
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Stress, Psychological / drug therapy*
  • Stress, Psychological / metabolism
  • Stress, Psychological / pathology


  • Antidepressive Agents, Second-Generation
  • Excitatory Amino Acid Transporter 2
  • Slc1a2 protein, rat
  • Fluoxetine