Ethanol withdrawal seizures produce increased c-fos mRNA in mouse brain

mRNA levels for the protooncogene c-fos, measured by Northern blot analysis, were greatly increased in brains of mice undergoing ethanol withdrawal seizures. This increase was transient (levels were increased at the time of the seizure and returned to normal by 24 hr or less after seizure) and was larger in hippocampus (40-fold) than in cerebral cortex (10-fold) or in cerebellum (6-fold). In mice that were fed ethanol chronically and withdrawn but that did not undergo overt withdrawal seizures, c-fos mRNA levels were not significantly increased. The findings with ethanol withdrawal seizures are similar in many respects to results of earlier studies with chemically induced seizures or kindling, which had led to the suggestion that c-fos expression may play a role in neuronal adaptation. The development of ethanol withdrawal seizures has been likened to kindling, and there is evidence indicating that ethanol withdrawal symptoms become more severe after repeated episodes of withdrawal. The present data support the hypothesis that this phenomenon may involve ethanol withdrawal seizure-induced increases in c-fos expression in various brain areas.