The role of group I mGlu receptors in the expression of ethanol-induced conditioned place preference and ethanol withdrawal seizures in rats

In animal models, N-methyl-d-aspartate (NMDA) receptors antagonists inhibit physical dependence and the reinforcing effects of ethanol. The group I metabotropic glutamate (mGlu) receptors antagonists (mGlu1 and mGlu5) attenuate excitatory effect of glutamate by functional modulation of the glutamate/NMDA receptors. The objective of the present study was to evaluate the effects of a selective mGlu5 receptors antagonist-MTEP, and mGlu1 receptors antagonist-EMQMCM, on two processes relevant to alcohol addiction: the expression of ethanol-induced conditioned place preference (CPP) paradigm, and ethanol withdrawal audiogenic seizures in rats. Our experiments indicated that EMQMCM at the doses of 5 and 10 mg/kg, and MTEP at the doses of 2.5 and 5 mg/kg, significantly attenuated the expression of ethanol CPP. Furthermore, both group I mGlu receptor antagonists, i.e. EMQMCM at the dose of 10 mg/kg and MTEP at the dose of 5 mg/kg, attenuated audiogenic seizures induced by the sound stimulus 12 h after withdrawal of ethanol in dependent rats. Our study shows the importance of mGlu5 and mGlu1 receptors for the expression of ethanol-induced CPP and withdrawal seizures, although mGlu5 receptors antagonist (MTEP) was more potent than the antagonist of mGlu1 receptors (EMQMCM).