We are engaged in a selective breeding program developing lines of mice which differ in severity of withdrawal convulsions after
ethanol treatment. Withdrawal seizure prone (WSP) mice show greater handling-induced convulsion scores than withdrawal seizure resistant (WSR) mice after 3 days of
ethanol intoxication. In the present experiments, we sought to characterize these mice further as a model of
genetic susceptibility to
ethanol dependence and withdrawal. During withdrawal after chronic treatment with
ethanol, WSP mice displayed more severe handling-induced convulsions and
tremor than WSR mice, and tended to show greater reduction of exploratory activity. WSP and WSR mice did not differ in
ethanol metabolism after acute treatment with
ethanol alone or after chronic treatment with
ethanol and
pyrazole, an
alcohol dehydrogenase inhibitor. Six to 10 hr after an acute injection of
ethanol, WSP and WSR mice showed elevated handling-induced convulsions. This elevation was more pronounced in WSP mice than in WSR mice. WSP mice also showed slightly more severe convulsions than WSR mice when treated with saline or
pyrazole alone. In summary, WSP and WSR mice treated with identical doses of
ethanol differ in several symptoms of withdrawal, whereas not differing in
ethanol metabolism. These mice constitute a useful population in which to study the molecular mechanisms of
ethanol dependence and withdrawal.