The role of mGluR5 on the therapeutic effects of ketamine in Wistar rats.
Psychopharmacology July 1, 2024 Dilan Gokalp, Gunes Unal
Ketamine's antidepressant effect requires suppressed activity of the metabotropic glutamate receptor 5 (mGluR5). In adult male Wistar rats, enhancing mGluR5 activity with the drug CDPPB blocked ketamine's antidepressant effect in the forced swim test without affecting locomotion. Combining a low dose of ketamine (1 mg/kg) with the mGluR5 antagonist MTEP produced a robust synergistic antidepressant effect. However, this combination eliminated the anxiolytic effect seen with either drug alone. The findings indicate that mGluR5 antagonism can boost ketamine's antidepressant effectiveness at low doses, but at the cost of its anxiety-reducing properties.