title: NMDA antagonist inhibits rapid tolerance to ethanol.
abstract: To test whether N-methyl-D-aspartate (NMDA) receptors have a role in the development of ethanol tolerance, (+)MK-801, an NMDA antagonist, and (-)MK-801, an inactive isomer, were tested in a rapid tolerance paradigm. Results showed that (+)MK-801 blocked the development of rapid tolerance to ethanol in the tilt-plane and hypothermia tests, while (-)MK-801 was ineffective. Neither drug changed the blood ethanol levels in the treated and untreated animals. These data suggest that the known role of NMDA receptors in long-term synaptic facilitation may underlie the effect of learning in the development of tolerance to the motor-impairing and hypothermic effects of ethanol.
authors.affiliation: Department of Pharmacology, University of Toronto, Canada.
authors.forename: J M
authors.initials: JM
authors.lastname: Khanna
authors.forename: P H
authors.initials: PH
authors.lastname: Wu
authors.forename: J
authors.initials: J
authors.lastname: Weiner
authors.forename: H
authors.initials: H
authors.lastname: Kalant
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004361:Drug Tolerance; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D007035:Hypothermia; D007536:Isomerism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate