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Preclinical Evaluation of Riluzole: Assessments of Ethanol Self‐Administration and Ethanol Withdrawal Symptoms

Background: Many of the neurobehavioral effects of ethanol are mediated by inhibition of excitatoryN‐methyl‐d‐aspartate (NMDA) and enhancement of inhibitory γ‐amino‐butyric‐acid (GABA) receptor systems. There is growing interest in drugs that alter these systems as potential medications for problems associated with alcoholism. The drug riluzole, approved for treatment of amyotrophic lateral sclerosis (ALS), inhibits NMDA and enhances GABAAreceptor system activity. This study was designed to determine the preclinical efficacy of riluzole to modulate ethanol self‐administration and withdrawal.Methods: Male C57BL/6J mice were trained to lever press on a concurrent fixed‐ratio 1 schedule of ethanol (10% v/v) versus water reinforcement during daily 16‐hour sessions. Riluzole (1 to 40 mg/kg, IP) was evaluated on ethanol self‐administration after acute and chronic (2 week) treatment. To determine if riluzole influences ethanol withdrawal‐associated seizures, mice were fed an ethanol‐containing or control liquid diet for 18 days. The effects of a single injection of riluzole (30 mg/kg) were examined on handling‐induced convulsions after ethanol withdrawal.Results: Acute riluzole (30 and 40 mg/kg) reduced ethanol self‐administration during the first 4 hours of the session, which corresponds to the known pharmacokinetics of this drug. Ethanol self‐administration was also reduced by riluzole after chronic treatment. Riluzole (30 mg/kg) significantly decreased the severity of ethanol‐induced convulsions 2 hours after ethanol withdrawal.Conclusions: These results demonstrate that riluzole decreases ethanol self‐administration and may reduce ethanol withdrawal severity in mice. Thus, riluzole may have utility in the treatment of problems associated with alcoholism.
- Center for Alcohol Studies Thailand
- UNC Lineberger Comprehensive Cancer Center United States
- UNC Lineberger Comprehensive Cancer Center United States
- Center for Alcohol Studies Thailand
- University of North Carolina at Chapel Hill United States
Male, Reinforcement Schedule, Riluzole, Alcohol Drinking, Dose-Response Relationship, Drug, Ethanol, Drug Evaluation, Preclinical, Self Administration, Alcohol Withdrawal Seizures, Mice, Inbred C57BL, Mice, Animals, Anticonvulsants
Male, Reinforcement Schedule, Riluzole, Alcohol Drinking, Dose-Response Relationship, Drug, Ethanol, Drug Evaluation, Preclinical, Self Administration, Alcohol Withdrawal Seizures, Mice, Inbred C57BL, Mice, Animals, Anticonvulsants
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