NMDA receptor antagonists inhibit ethanol-produced locomotor stimulation in NMRI mice.
The effects of competitive and noncompetitive NMDA receptor antagonists on locomotor stimulation produced by low doses of ethanol were studied in NMRI mice. Both competitive (CGP 39551) and noncompetitive (MK-801) NMDA receptor antagonists inhibited ethanol-produced behavioral stimulation in doses which by themselves had no effects on the locomotor activity. In additional experiments, where the muscle relaxant actions of ethanol and the NMDA receptor antagonists were studied, it was found that the "inhibitory" effects of the NMDA receptor antagonists in the locomotor activity test situation most likely were due to a potentiation of the sedative effects of ethanol and/or the antagonists. The implications of the current observations with regard to previously reported results concerning interactions between ethanol and NMDA receptor antagonists and with regard to a possible therapeutic advantage of using competitive NMDA receptor antagonists in the management of the human alcohol abstinence syndrome are discussed.
Liljequist
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Department of Drug Dependence Research, Karolinska Institute, Stockholm, Sweden.
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*
D016194:Receptors, N-Methyl-D-Aspartate; C064540:CGP 39551; D000431:Ethanol; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate