Ethanol and diazepam withdrawal convulsions are extensively codetermined in WSP and WSR mice

Life Sci. 1989;44(26):2075-80. doi: 10.1016/0024-3205(89)90354-8.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Diazepam
  • Ethanol
  • Flumazenil / pharmacology
  • Mice
  • Mice, Inbred Strains
  • Seizures / genetics*
  • Substance Withdrawal Syndrome / genetics*
  • Substance-Related Disorders / physiopathology

Substances

  • Ethanol
  • Flumazenil
  • Diazepam