N-methyl-D-aspartate and group I metabotropic glutamate receptors are involved in the expression of ethanol-induced sensitization in mice.

Effects of acamprosate and ionotropic uncompetitive N-methyl-D-aspartate receptor antagonists and group I metabotropic glutamatergic receptor antagonists on the expression of ethanol-induced sensitization were investigated in mice. The results indicated that acamprosate (200 and 400 mg/kg) and N-methyl-D-aspartate receptor antagonists, neramexane (10 and 20 mg/kg) and MK-801 (0.1 and 0.2 mg/kg), inhibited the expression of ethanol-induced sensitization. Acamprosate, but not the other compounds tested, also blocked the stimulant effect of acute injections of ethanol. Among the group I metabotropic glutamatergic receptor antagonists, only the metabotropic glutamatergic receptor 5 antagonist, MTEP (5, 10, and 20 mg/kg) showed an effect similar to the N-methyl-D-aspartate receptor antagonists. The metabotropic glutamatergic receptor 1 antagonist, EMQMCM (5, 10, and 20 mg/kg), however, potentiated the inhibitory effect of MK-801 on the expression of ethanol-induced sensitization. The findings indicate that glutamatergic neurotransmission is important in the ethanol-induced sensitization process, and suggest that co-administration of metabotropic glutamatergic receptor 1 antagonists and N-methyl-D-aspartate receptor antagonists may be useful in therapy for alcoholism.