Belknap J K, Crabbe J C, Laursen S E
Department of Medical Psychology, Oregon Health Sciences University, Portland.
Life Sci. 1989;44(26):2075-80. doi: 10.1016/0024-3205(89)90354-8.
Selective breeding was used to produce lines of mice which differ markedly in their genetically-mediated vulnerability to handling-induced convulsions (HIC) associated with the ethanol withdrawal syndrome. These are known as the ethanol withdrawal seizure prone (WSP) and withdrawal seizure resistant (WSR) selection lines. As a result of 5 generations of selective breeding with ethanol, a 3.4-fold difference between WSP and WSR mice was seen in HIC associated with ethanol withdrawal. When diazepam was used as the dependence-producing drug, a 2.4-fold difference emerged. After 6 more generations of selective breeding with ethanol, an approximate 10-fold difference was seen with ethanol, while with diazepam, this difference in HIC scores was also about 10-fold. This close parallel between ethanol and diazepam indicates that physical dependence on both drugs, as indexed by handling-induced convulsions, is extensively codetermined by the same genes, and thus by the same mechanisms, in these selectively-bred mice.
选择性育种被用于培育出在与乙醇戒断综合征相关的由基因介导的对处理诱导惊厥（HIC）的易感性方面有显著差异的小鼠品系。这些被称为乙醇戒断惊厥易感（WSP）和戒断惊厥抗性（WSR）选择品系。经过5代用乙醇进行的选择性育种，在与乙醇戒断相关的HIC中，WSP和WSR小鼠之间出现了3.4倍的差异。当使用地西泮作为产生依赖性的药物时，出现了2.4倍的差异。在用乙醇再进行6代选择性育种后，乙醇导致的差异约为10倍，而使用地西泮时，HIC评分的这种差异也约为10倍。乙醇和地西泮之间的这种紧密平行关系表明，在这些选择性育种的小鼠中，由处理诱导惊厥所衡量的对这两种药物的身体依赖性在很大程度上是由相同的基因以及相同的机制共同决定的。
