In conclusion, in this study, we found that the group II mGlu receptor antagonist LY341495 enhances the antidepressant-like effect of ketamine in the behavioral despair model of depression, indicating that the therapeutic dose of ketamine could be markedly reduced by its co-administration with LY341495 (a mGlu2/3 antagonist). The gene discussed is GRM2; the disease is depressive symptom measurement.