Chronic Simvastatin Treatments Attenuate Ethanol Withdrawal Syndrome in Rats

Abstract

Rodent models of ethanol withdrawal-induced anxiety have been used to explore the neurobiology underlying withdrawal and to evaluate the utility of therapeutic agents aimed at reducing withdrawal severity. Of the many tests of anxiety-like behavior, the elevated plus maze and open field are the most commonly used. In general, ethanol withdrawal decreases most or all of the individual behaviors recorded in these tasks, indicating the occurrence of an anxiogenic-like effect of withdrawal in rodents. Effects of sub-chronic simvastatin treatments on ethanol withdrawal syndrome were inves- tigated in rats. Ethanol (7.2% v/v) was given to adult male Wistar rats by a liquid diet for 30 days. Sub-chronic (once daily) simvastatin (1 or 10 mg/kg) or saline were administered to rats by oral gavage. After 24 hours of ethanol withdrawal on the simvastatin treatment rats were observed in behavior tests. The increases the time open arms entries in the elevated plus-maze and grooming in the open-field through the exposure to sub-chronic treatment with simvastatin in rats submitted to ethanol intake, indicating beneficial effects on ethanol withdrawal syndrome. Our results suggest that sub-chronic simvastatin treatment attenuates ethanol withdrawal syndrome in ethanol-dependent rats and this drug may be useful for treatment of ethanol-type dependence.