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Flumazenil (Ro15-1788) does not affect ethanol tolerance and dependence.
A W Chan1, F W Leong, D L Schanley
1Research Institute on Alcoholism, New York State Division of Alcoholism and Alcohol Abuse, Buffalo 14203.
Pharmacology, Biochemistry, and Behavior
|July 1, 1991
Summary
Flumazenil (Ro15-1788) does not appear to reduce the central effects or withdrawal symptoms associated with chronic ethanol exposure in mice. This study found no significant impact on ethanol tolerance or dependence.
Area of Science:
- Neuroscience
- Pharmacology
- Addiction Research
Background:
- Conflicting reports exist regarding flumazenil's ability to counteract ethanol's central effects.
- Understanding flumazenil's role in ethanol dependence is crucial for potential therapeutic interventions.
Purpose of the Study:
- To investigate the efficacy of flumazenil (Ro15-1788) in antagonizing ethanol's central effects and withdrawal symptoms.
- To determine if flumazenil affects ethanol tolerance and dependence in a mouse model.
Main Methods:
- C57BL/6J mice were chronically administered an ethanol liquid diet or a control diet.
- Flumazenil (Ro15-1788) or vehicle was administered at various time points before ethanol withdrawal.
- Withdrawal seizures, hypothermia, ataxia (sleep time, horizontal dowel tests), and ethanol tolerance were assessed.
Main Results:
- Flumazenil did not attenuate handling-induced withdrawal seizures or hypothermia in ethanol-dependent mice.
- Flumazenil did not abolish or reduce tolerance to ethanol's ataxic and hypothermic effects during withdrawal.
Conclusions:
- Flumazenil (25 mg/kg) demonstrated no effect on ethanol tolerance and dependence in this experimental model.
- The findings suggest flumazenil is ineffective in mitigating ethanol withdrawal symptoms or altering ethanol tolerance.