The mGluR5 antagonist MPEP suppresses the expression and reinstatement, but not the acquisition, of the ethanol-conditioned place preference in mice.

The glutamatergic system may play a vital role in regulating neurobehavioral effects of various drugs of abuse. In the present study, we evaluated the effects of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a selective antagonist of the type 5 metabotropic glutamate receptor (mGluR5) on the acquisition, expression and reinstatement of ethanol conditioned place preference (CPP). In the ethanol acquisition study, mice were conditioned with saline or ethanol (20% v/v, 2g/kg) on alternating days for 8 consecutive days and were given MPEP 10 min before ethanol conditioning. In another experiment, animals were conditioned with 2g/kg ethanol and MPEP was administered 10 min prior to the post-conditioning test. In a reinstatement study, following the extinction phase, animals were pretreated with MPEP 10 min prior to a priming injection of 1.0 g/kg ethanol. The mGluR5 antagonist MPEP significantly reduced the expression and the reinstatement in dose-dependent manner, but not acquisition of ethanol-induced CPP. These results indicate that mGluR5 may be involved in the expression and reinstatement of conditioned rewarding effects of ethanol, but not the acquisition of ethanol, which provide an evidence that mGluR5 blockade might make dissociable contributions during the training (acquisition phase), the performance of behavior (expression phase) and reinstatement.