NMDA antagonist inhibits rapid tolerance to ethanol.
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.
Khanna
J M
JM
Department of Pharmacology, University of Toronto, Canada.
Wu
P H
PH
Weiner
J
J
Kalant
H
H
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*
D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate