Male mGlu5 knockout (KO) and wild-type (WT) control mice were subjected to a forced swim test (FST) and pre-treated with either 0, 10, or 30 mg/kg of MPEP 15 minutes prior. MPEP produced a dose-dependent reduction in immobility in the FST after acute administration. Statistically significant reductions in the duration of immobility were detected at a dose of 30 mg/kg. The maximal reduction of immobility produced by MPEP was comparable with that produced by 15 mg/kg imipramine. When 5 mg/kg MPEP was administered daily for five consecutive days and tested for activity in the FST after dosing on day 5, MPEP significantly reduced immobility as with acute dosing

Rat cortical neuronal cells cultured in 96-well plates at 7–8 DIV were pretreated for 30 min with 0.2–200 μm of the mGluR5 antagonists MPEP, with or without MK801 following the addition of 150 μm Na-glutamate or 50 μm NMDA. After 24 h of incubation with drugs, cell viability was tested by measuring LDH release, using a CytoTox 96 non-radioactive cytotoxicity assay kit. LDH release based cell viability assay revealed significant neuroprotective effects of MPEP both in glutamate- and NMDA-treated cultures. Neuroprotection was observed at concentrations of 20 micro-M MPEP and above.