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Alcohol and Alcoholism Advance Access originally published online on April 24, 2006
Alcohol and Alcoholism 2006 41(4):399-406; doi:10.1093/alcalc/agl029
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© The Author 2006. Published by Oxford University Press on behalf of the Medical Council on Alcohol. All rights reserved

PREGABALIN IS EFFECTIVE AGAINST BEHAVIORAL AND ELECTROGRAPHIC SEIZURES DURING ALCOHOL WITHDRAWAL

HOWARD C. BECKER1,2,3,*, HUGH MYRICK1,2,3 and LYNN M. VEATCH1,2,3

1 Charleston Alcohol Research Center, Center for Drug and Alcohol Programs, Institute of Psychiatry, Charleston, SC, USA, 2 Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA and 3 Department of Veterans Affairs, Ralph H. Johnson VA Medical Center, Charleston, South Carolina, USA

* Author to whom correspondence should be addressed at: Charleston Alcohol Research Center, Center for Drug and Alcohol Programs, Institute of Psychiatry, 67 President Street, Charleston, SC 29425, USA. Tel.: +1 843 792 5207; Fax: +1 843 792 5204; E-mail: beckerh{at}musc.edu

(Received 25 July 2005; first review notified 23 August 2005; in revised form 21 March 2006; accepted 21 March 2006)

Aims: Pregabalin has been shown to possess anticonvulsant, analgesic, and anxiolytic properties in a variety of testing situations. This study was designed to evaluate the ability of pregabalin to exert its anticonvulsant effects against behavioral and electrographic measures of CNS hyperexcitability associated with alcohol withdrawal in a mouse model of ethanol dependence. Methods: Adult mice were chronically exposed to ethanol and, upon withdrawal, were tested for behavioral signs of seizure activity (handling-induced convulsions) or abnormalities in spontaneous EEG activity recorded from cortical and subcortical sites. Results: Pregabalin (50–200 mg/kg) administered 1 and 4 h into withdrawal dose dependently reduced severity of handling-induced convulsions in comparison to vehicle-treated mice. Similarly, pregabalin reduced the frequency in which EEG activity was interrupted by trains of high-voltage synchronous activity in a dose-related fashion. Finally, pregabalin treatment of repeated withdrawals was effective in blocking the development of withdrawal sensitization observed in vehicle-treated mice. Conclusions: Collectively, these results suggest that pregabalin may be an effective therapeutic agent for medical management of alcohol detoxification.


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