Pregabalin is effective against behavioral and electrographic seizures during alcohol withdrawal.
OBJECTIVE
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.
Becker
Howard C
HC
Charleston Alcohol Research Center, Center for Drug and Alcohol Programs, Institute of Psychiatry, 67 President Street, Charleston, SC 29425, USA. beckerh@musc.edu
Myrick
Hugh
H
Veatch
Lynn M
LM
D000280:Administration, Inhalation; D020270:Alcohol Withdrawal Seizures / Q000188:drug therapy*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects*; D000431:Ethanol / Q000633:toxicity; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D000069583:Pregabalin; D012815:Signal Processing, Computer-Assisted; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
D000927:Anticonvulsants; D000431:Ethanol; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid