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Anesth Analg 2006;103:117-120
© 2006 International Anesthesia Research Society
doi: 10.1213/01.ane.0000220944.27963.b1

ANESTHETIC PHARMACOLOGY

Ethanol-Induced Hypnotic Tolerance Is Absent in N-Methyl-d-Aspartate Receptor {varepsilon}1 Subunit Knockout Mice

Yuki Sato, MD, PhD, Norimasa Seo, MD, PhD, and Eiji Kobayashi, MD, PhD

From the Department of Anesthesiology, Divisions of Organ Replacement Research, Center for Molecular Medicine, Jichi Medical School, Tochigi, Japan.

Recent pharmacological studies suggest that N-methyl-d-aspartate (NMDA) receptors play an important role in neuroadaptive processes in the development of tolerance to addictive drugs, such as opioids, amphetamine, and cocaine. In the present study, we investigated the contribution of the NMDA receptor to ethanol-induced hypnotic tolerance using NMDA receptor {varepsilon}1 subunit knockout mice. Hypnotic sensitivity to a single injection of 3, 3.5, and 4 g/kg ethanol was not significantly different between wild-type mice and NMDA receptor {varepsilon}1 subunit knockout mice. In contrast, although wild-type mice displayed hypnotic tolerance after repeated administration of 4 g/kg ethanol for 4 consecutive days, no change in the duration of hypnosis was observed in knockout mice. No significant differences were observed in blood ethanol clearance between wild-type and knockout mice on day 4. Our results indicate {varepsilon}1 subunit containing the NMDA receptor might be involved in the development of ethanol-induced hypnotic tolerance.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2006 by the International Anesthesia Research Society.