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.
Boyce-Rustay
Janel M
JM
Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA. boycej@mail.nih.gov
Holmes
Andrew
A
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002492:Central Nervous System Depressants / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010636:Phenols / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D012890:Sleep / Q000187:drug effects*
D002492:Central Nervous System Depressants; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D010636:Phenols; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C109643:Ro 25-6981; C064539:2-amino-4-methyl-5-phosphono-3-pentenoic acid; D000431:Ethanol; D015763:2-Amino-5-phosphonovalerate