Alcohol and Alcoholism Advance Access published online on June 4, 2007
Alcohol and Alcoholism, doi:10.1093/alcalc/agm047
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The Author 2007. Published by Oxford University Press on behalf of the Medical Council on Alcohol.
Topiramate (Topamax) Reduces Conditioned Abstinence Behaviours and Handling-Induced Convulsions (HIC) after Chronic Administration of Alcohol in Swiss-Webster MICE
1 Department of Psychology, Kastle Hall, University of Kentucky, Lexington, Kentucky-40506, USA
2 Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky-40536, USA
* Author to whom correspondence should be addressed at: Department of Psychology, Kastle Hall, University of Kentucky, Lexington, Kentucky-40506, USA. Tel: +1 859-257 6122; Fax: +1 859-323 1979; E-mail: justinfarook{at}uky.edu
Received 19 February 2007; first review notified 17 April 2007; in revised form 3 May 2007; accepted 11 May 2007
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Abstract |
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Topiramate has emerged as one of the promising drugs for the treatment of alcoholism and alcohol addiction. Recent studies have shown that topiramate reduces harmful drinking and initiates abstinence in humans, but little is known as to why this drug is effective. Aims: In the present study, we examined the effects of topiramate in reducing convulsions during alcohol withdrawal using a procedure called the handling-induced convulsion (HIC) test in male Swiss-Webster mice. In addition, we examined the ability of topiramate to reduce alcohol conditioned and anxiety related behaviours during conditioned abstinence using the elevated plus maze (EPM) test. Methods: HICs were examined 10 h after the 3rd daily alcohol (2.5 g/kg; 20% w/v) + 4 methylpyrazole (4MP) (9 mg/kg) intraperitoneal (i.p.) injection with topiramate (0, 10 or 20 mg/kg ip) administered 30 min before testing. In the EPM, alcohol (1.75 g/kg; 20%, i.p.) or saline was administered daily for 9 days and subjects were immediately placed on the maze. Anxiety related behaviours included the amount of time spent and number of entries in the open or closed arms and grooming bouts, and conditioned behaviours including the stretched-attend posture were examined 24 h after the last day of alcohol injection. Results: Topiramate (10 and 20 mg/kg) significantly reduced HIC scores (P < 0.05) compared to the alcohol/saline group. In the EPM, topiramate (20 mg/kg) reduced the stretched-attend postures (P < 0.001) compared to the alcohol/saline group. Conclusion: These findings suggest that topiramate reduces HICs during alcohol withdrawal and alcohol-conditioned behaviours during conditioned abstinence in Swiss-Webster mice.