Kosobud A, Crabbe J C
J Pharmacol Exp Ther. 1986 Jul;238(1):170-7.
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.
我们正在开展一项选择性育种计划，培育经乙醇处理后戒断惊厥严重程度不同的小鼠品系。乙醇中毒3天后，易发生戒断惊厥（WSP）的小鼠比抗戒断惊厥（WSR）的小鼠表现出更高的处理诱导惊厥评分。在本实验中，我们试图将这些小鼠进一步表征为乙醇依赖和戒断遗传易感性的模型。在乙醇慢性治疗后的戒断期间，WSP小鼠比WSR小鼠表现出更严重的处理诱导惊厥和震颤，并且倾向于表现出更大程度的探索活动减少。单独用乙醇急性治疗或用乙醇和酒精脱氢酶抑制剂吡唑慢性治疗后，WSP和WSR小鼠在乙醇代谢方面没有差异。急性注射乙醇6至10小时后，WSP和WSR小鼠的处理诱导惊厥有所增加。这种增加在WSP小鼠中比在WSR小鼠中更明显。单独用生理盐水或吡唑处理时，WSP小鼠也比WSR小鼠表现出稍严重的惊厥。总之，用相同剂量乙醇处理的WSP和WSR小鼠在几种戒断症状上存在差异，而在乙醇代谢方面没有差异。这些小鼠构成了一个有用的群体，可用于研究乙醇依赖和戒断的分子机制。
