ly-341495 and Depressive-Disorder--Treatment-Resistant

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.

Topics: Amino Acids; Animals; Corticosterone; Depressive Disorder, Treatment-Resistant; Disease Models, Animal; Drug Administration Schedule; Immobility Response, Tonic; Injections, Subcutaneous; Ketamine; Male; Rats; Receptors, Metabotropic Glutamate; Xanthenes