Reduced expression of glutamate transporters vGluT1, EAAT2 and EAAT4 in learned helpless rats, an animal model of depression

Neuropharmacology. 2010 Feb;58(2):465-73. doi: 10.1016/j.neuropharm.2009.09.005. Epub 2009 Sep 9.


Background: It has been widely accepted that glial pathology and disturbed synaptic transmission contribute to the neurobiology of depression. Apart from monoaminergic alterations, an influence of glutamatergic signal transduction has been reported. Therefore, gene expression of glutamate transporters that strictly control synaptic glutamate concentrations have to be assessed in animal models of stress and depression.

Methods: We performed in situ-hybridizations in learned helplessness rats, a well established animal model of depression, to assess vGluT1 and EAAT1-4. Sprague-Dawley rats of two inbred lines were tested for helpless behavior and grouped into three cohorts according to the number of failures to stop foot shock currents by lever pressing.

Results: Helpless animals showed a significantly suppressed expression of the glial glutamate transporter EAAT2 (rodent nomenclature GLT1) in hippocampus and cerebral cortex compared to littermates with low failure rate and not helpless animals. This finding was validated on protein level using immunohistochemistry. Additionally, expression levels of EAAT4 and the vesicular transporter vGluT1 were reduced in helpless animals. In contrast, the transcript levels of EAAT1 (GLAST) and EAAT3 (EAAC1) were not significantly altered.

Conclusions: These results strongly suggest reduced astroglial glutamate uptake and implicate increased glutamate levels in learned helplessness. The findings are in concert with antidepressant effects of NMDA-receptor antagonists and the hypotheses that impaired astroglial functions contribute to the pathogenesis of affective disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism*
  • Cerebral Cortex / metabolism
  • Depressive Disorder / metabolism*
  • Disease Models, Animal
  • Excitatory Amino Acid Transporter 1 / metabolism
  • Excitatory Amino Acid Transporter 2 / metabolism*
  • Excitatory Amino Acid Transporter 3 / metabolism
  • Excitatory Amino Acid Transporter 4 / metabolism*
  • Helplessness, Learned*
  • Hippocampus / metabolism
  • Male
  • Rats
  • Rats, Inbred Strains
  • Rats, Sprague-Dawley
  • Vesicular Glutamate Transport Protein 1 / metabolism*


  • Excitatory Amino Acid Transporter 1
  • Excitatory Amino Acid Transporter 2
  • Excitatory Amino Acid Transporter 3
  • Excitatory Amino Acid Transporter 4
  • Slc17a7 protein, rat
  • Slc1a1 protein, rat
  • Slc1a2 protein, rat
  • Slc1a3 protein, rat
  • Slc1a6 protein, rat
  • Vesicular Glutamate Transport Protein 1