Effects of ketamine and LY341495 on the depressive-like behavior of repeated corticosterone-injected rats

Pharmacol Biochem Behav. 2013 Jun:107:20-3. doi: 10.1016/j.pbb.2013.03.017. Epub 2013 Apr 9.


In the present study, to further validate repeated corticosterone (CORT)-treated rats as a treatment-resistant depression (TRD) model, we first examined the effect of ketamine, which is known to be effective for the treatment of TRD, on the depressive-like behavior of CORT-treated rats. In this model, ketamine significantly reduced the increased immobility time of CORT-treated rats during the forced swim test (FST), indicating that its efficacy against TRD could be detected using this model. We next examined the effect of LY341495, a group ΙΙ metabotropic glutamate (mGlu2/3) receptor antagonist, in this model to evaluate its potential for the alleviation of TRD. LY341495, similar to ketamine, attenuated the increased immobility time of CORT-treated rats during the FST. Therefore, these results suggest that mGlu2/3 receptor antagonists might be effective for patients with depression, including TRD.

Publication types

  • Validation Study

MeSH terms

  • Amino Acids / pharmacology
  • Amino Acids / therapeutic use*
  • Animals
  • Corticosterone / administration & dosage
  • Corticosterone / adverse effects*
  • Depressive Disorder, Treatment-Resistant / drug therapy*
  • Disease Models, Animal
  • Drug Administration Schedule
  • Immobility Response, Tonic / drug effects
  • Injections, Subcutaneous
  • Ketamine / pharmacology
  • Ketamine / therapeutic use*
  • Male
  • Rats
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Xanthenes / pharmacology
  • Xanthenes / therapeutic use*


  • Amino Acids
  • LY 341495
  • Receptors, Metabotropic Glutamate
  • Xanthenes
  • Ketamine
  • Corticosterone