Ethanol and diazepam withdrawal convulsions are extensively codetermined in WSP and WSR mice.
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.
Belknap
J K
JK
Department of Medical Psychology, Oregon Health Sciences University, Portland.
Crabbe
J C
JC
Laursen
S E
SE
D000818:Animals; D003975:Diazepam; D000431:Ethanol; D005442:Flumazenil / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D012640:Seizures / Q000235:genetics*; D013375:Substance Withdrawal Syndrome / Q000235:genetics*; D019966:Substance-Related Disorders / Q000503:physiopathology
D000431:Ethanol; D005442:Flumazenil; D003975:Diazepam