Effect of NMDA antagonists, an NMDA agonist, and serotonin depletion on acute tolerance to ethanol.
The effect of N-methyl-D-aspartate (NMDA) antagonists [dizocilpine, (+)MK-801, and ketamine], an NMDA agonist (D-cycloserine) and of brain serotonin (5-HT) depletion with p-chlorophenylalanine (p-CPA) on acute tolerance to ethanol was examined, using the tolerance model proposed by Radlow [Psychopharmacology 114 (1994) 1-8] and Martin and Moss [Alcohol Clin Exp Res 17 (1993) 211-216]. This model is based on the concept of a linear increase of acute tolerance with time; the rate of acute tolerance development is the slope of the output function that relates blood alcohol concentrations (BACs) and intoxication. Pretreatment with NMDA antagonists inhibited the development of acute tolerance to ethanol, whereas pretreatment with D-cycloserine enhanced it. Depletion of 5-HT by p-CPA also blocked acute tolerance to ethanol. These results on acute tolerance are similar to those previously found on rapid and chronic tolerance to ethanol.
Khanna
J M
JM
Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
Morato
G S
GS
Kalant
H
H
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance / Q000502:physiology*; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D012701:Serotonin / Q000172:deficiency*
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D012701:Serotonin; D000431:Ethanol