Flumazenil (Ro15-1788) does not affect ethanol tolerance and dependence

Flumazenil (Ro15-1788) does not affect ethanol tolerance and dependence

There are conflicting reports concerning whether flumazenil (Ro15-1788) can antagonize the central effects of ethanol and ethanol withdrawal reactions. C57BL/6J mice were treated chronically with an ethanol liquid diet. Control mice were pair fed an isocaloric diet containing no ethanol. These mice...

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Bibliographic Details
Published in:Pharmacology, biochemistry and behavior Vol. 39; no. 3; p. 659
Main Authors: Chan, A W, Leong, F W, Schanley, D L, Langan, M C, Penetrante, F
Format: Journal Article
Language:English
Published: United States 01-07-1991
Subjects:
Animals
Ataxia - chemically induced
Ataxia - prevention & control
Behavior, Animal - drug effects
Body Temperature - drug effects
Diet
Drug Tolerance
Ethanol - administration & dosage
Ethanol - pharmacology
Flumazenil - pharmacology
Handling (Psychology)
Injections, Intraperitoneal
Male
Mice
Mice, Inbred C57BL
Seizures - etiology
Substance Withdrawal Syndrome - psychology
Substance-Related Disorders - psychology
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Summary:There are conflicting reports concerning whether flumazenil (Ro15-1788) can antagonize the central effects of ethanol and ethanol withdrawal reactions. C57BL/6J mice were treated chronically with an ethanol liquid diet. Control mice were pair fed an isocaloric diet containing no ethanol. These mice were injected with either Ro15-1788 (25 mg/kg) or vehicle immediately before, 14 h or 24 h before ethanol withdrawal. Under these conditions, no attenuation of the severity of handling-induced withdrawal seizures or of withdrawal hypothermia was observed in the ethanol-dependent mice injected with Ro15-1788. Likewise, there was no abolition or attenuation of tolerance to the ataxic effects (sleep time and horizontal dowel tests) and hypothermic effects of ethanol by Ro15-1788 when the mice were tested on day 3 of ethanol withdrawal. It is concluded that Ro15-1788 (25 mg/kg) has no effect on ethanol tolerance and dependence.
ISSN:0091-3057
DOI:10.1016/0091-3057(91)90143-P