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The NMDA receptor antagonist dizocilpine differentially affects environment-dependent and environment-independent ethanol tolerance

The NMDA receptor antagonist dizocilpine differentially affects environment-dependent and... 213 113 113 3 4 Gyula Szabó Boris Tabakoff Paula L. Hoffman Department of Pharmacology, C236 University of Colorado Health Sciences Center 4200 E. 9th Ave. 80262 Denver CO USA Department of Pathophysiology Albert Szent-Györgyi Medical University H-6701 Szeged Hungary Abstract Antagonists of the N -methyl-D-aspartate subtype of glutamate receptor have been reported to block the development of tolerance to various effects of ethanol and opiates, using paradigms in which tolerance is believed to be governed by learning. There is considerable evidence to implicate the N -methyl-D-aspartate receptor in learning processes, and therefore the ability of the antagonists to block tolerance has been attributed to their effects on learning. To evaluate this hypothesis, we compared, in C57BL/6 mice, the effect of the uncompetitive N -methyl-D-aspartate receptor antagonist, dizocilpine, on environment-dependent (associative) tolerance to ethanol, which is governed by learning, and on environment-independent (nonassociative) ethanol tolerance, in which learning plays a minimal role. Environment-dependent tolerance was induced by repeated ethanol injections, and dizocilpine blocked the development of this type of tolerance to the hypothermic and incoordinating effects of ethanol. In contrast, when environment-independent ethanol tolerance was induced by feeding the mice an ethanol-containing liquid diet, dizocilpine treatment had no effect on the development of tolerance to the hypothermic, incoordinating or hypnotic effects of ethanol. The results support the hypothesis that the effect of N-methyl-D-aspartate receptor antagonists on ethanol tolerance reflects the more general role of this receptor in processes involving learning and memory. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Psychopharmacology Springer Journals

The NMDA receptor antagonist dizocilpine differentially affects environment-dependent and environment-independent ethanol tolerance

Szabó, Gyula; Tabakoff, Boris; Hoffman, Paula
Psychopharmacology , Volume 113 (3) – Jan 1, 1994
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References (43)

Publisher
Springer Journals
Copyright
Copyright © 1994 by Springer-Verlag
Subject
Biomedicine; Pharmacology/Toxicology; Psychiatry
ISSN
0033-3158
eISSN
1432-2072
DOI
10.1007/BF02245231
Publisher site
See Article on Publisher Site

Abstract

213 113 113 3 4 Gyula Szabó Boris Tabakoff Paula L. Hoffman Department of Pharmacology, C236 University of Colorado Health Sciences Center 4200 E. 9th Ave. 80262 Denver CO USA Department of Pathophysiology Albert Szent-Györgyi Medical University H-6701 Szeged Hungary Abstract Antagonists of the N -methyl-D-aspartate subtype of glutamate receptor have been reported to block the development of tolerance to various effects of ethanol and opiates, using paradigms in which tolerance is believed to be governed by learning. There is considerable evidence to implicate the N -methyl-D-aspartate receptor in learning processes, and therefore the ability of the antagonists to block tolerance has been attributed to their effects on learning. To evaluate this hypothesis, we compared, in C57BL/6 mice, the effect of the uncompetitive N -methyl-D-aspartate receptor antagonist, dizocilpine, on environment-dependent (associative) tolerance to ethanol, which is governed by learning, and on environment-independent (nonassociative) ethanol tolerance, in which learning plays a minimal role. Environment-dependent tolerance was induced by repeated ethanol injections, and dizocilpine blocked the development of this type of tolerance to the hypothermic and incoordinating effects of ethanol. In contrast, when environment-independent ethanol tolerance was induced by feeding the mice an ethanol-containing liquid diet, dizocilpine treatment had no effect on the development of tolerance to the hypothermic, incoordinating or hypnotic effects of ethanol. The results support the hypothesis that the effect of N-methyl-D-aspartate receptor antagonists on ethanol tolerance reflects the more general role of this receptor in processes involving learning and memory.

Journal

Psychopharmacology – Springer Journals

Published: Jan 1, 1994

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