Functional roles of NMDA receptor NR2A and NR2B subunits in the acute intoxicating effects of ethanol in mice

The present study examined the roles of NR2A and NR2B subunit‐containing NMDA receptors in the mediation of the sedative/hypnotic effects of ethanol in mice. The ability of the competitive NMDA antagonist, CGP‐37849 (0, 1, or 3 mg/kg), and the NR2B‐selective antagonist, Ro 25‐6981 (0, 3, or 10 mg/kg), to alter (3 g/kg) ethanol‐induced sleep time was measured in C57BL/6J mice and NR2A knockout (KO) mice. The results show that pretreatment with either antagonist significantly potentiated the sedative/hypnotic effects of ethanol in C57BL/6J mice. These effects were not significantly altered in NR2A KO mice. Basal sleep time responses to ethanol were also normal in NR2A KO mice. These findings confirm a major role for NMDA receptors in the acute intoxicating actions of ethanol and provide tentative support for a prepotent role of the NR2B subunit in these effects. Synapse 56:222–225, 2005. Published 2005 Wiley‐Liss, Inc.