Ethanol and barbiturate withdrawal convulsions are extensively codetermined in mice.
Selective breeding was used to produce lines of mice which differ markedly from one another in ethanol physical dependence development as indexed by handling-induced convulsions (HIC) induced by withdrawal from ethanol. These are known as the Withdrawal Seizure Prone (WSP) and Withdrawal Seizure Resistant (WSR) selected lines. Mice selectively-bred for severe HIC (Withdrawal Seizure Prone lines) exhibited 3-fold greater HIC scores than did mice selectively-bred for mild HIC (Withdrawal Seizure Resistant lines) after five generations of selective-breeding. When phenobarbital was used as the dependence-producing drug rather than ethanol, the WSP vs. WSR differences in HIC were similar to those seen with ethanol. This implies that a high degree of commonality exists between ethanol and phenobarbital in the determinants of this commonly used index of physical dependence. Both WSP and WSR mice showed equivalent brain phenobarbital concentrations and equal functional tolerance development as indexed by several measures of impairment.
Belknap
J K
JK
Department of Pharmacology, School of Medicine, University of North Dakota, Grand Forks 58202.
Danielson
P W
PW
Lame
M
M
Crabbe
J C
JC
D000818:Animals; D004361:Drug Tolerance; D000431:Ethanol / Q000009:adverse effects* / Q000378:metabolism; D007035:Hypothermia / Q000139:chemically induced / Q000235:genetics; D051379:Mice; D010634:Phenobarbital / Q000009:adverse effects* / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced* / Q000235:genetics; D013375:Substance Withdrawal Syndrome / Q000235:genetics*
D000431:Ethanol; D010634:Phenobarbital