The group II mGlu receptor antagonist LY341495 induces a rapid antidepressant-like effect and enhances the effect of ketamine in the chronic unpredictable mild stress model of depression in C57BL/6J mice.
Progress in Neuro-psychopharmacology and Biological Psychiatry January 2, 2021 A. Pałucha-poniewiera, K. Podkowa, A. Rafało-ulińska
The mGlu2/3 receptor antagonist LY341495 produced a dose-dependent antidepressant-like effect in mice exposed to chronic unpredictable mild stress, after both a single dose and three daily doses. Combining a low, ineffective dose of LY341495 with a low, ineffective dose of ketamine reversed stress-induced behavioral deficits, suggesting the combination could lower ketamine's therapeutic dose. The combination activated the mTOR pathway and did not cause hyperactivity, memory impairment, or motor coordination problems that occur with a higher ketamine dose. The findings indicate mGlu2/3 receptor antagonists may safely reduce the effective dose of ketamine.