Possible pleiotropic effects of genes specifying sedative/hypnotic sensitivity to ethanol on other alcohol-related traits.
BACKGROUND
Initial sensitivity to ethanol is a predictor of alcohol abuse that has been studied extensively in both human and animal populations. Selection for initial sensitivity to the sedative/hypnotic effects of ethanol resulted in the long-sleep and short-sleep lines of mice. Some of the genes selected in these lines could also specify differential responses in other ethanol-related phenotypes and, perhaps, for other drugs of abuse. We assessed congenic mice carrying a single quantitative trait locus (QTL) from the inbred long-sleep (ILS) or inbred short-sleep (ISS) strain on the reciprocal background for a number of ethanol- and pentobarbital-related phenotypes.


METHODS
Each congenic strain was tested for ethanol elimination rates at 4.1 g/kg, ethanol-induced ataxia at 2.0 g/kg, ethanol-induced hypothermia at 4.1 g/kg, and pentobarbital-induced loss of righting reflex (LORR) at 60 mg/kg. Additionally, the ILS.ISS congenics were tested for low-dose ethanol-induced activation (LDA) at five doses ranging from 0.6 to 1.2 g/kg ethanol, and the ISS.ILS congenics were tested for LDA at 1.8 g/kg of ethanol.


RESULTS
There was little difference in the ethanol elimination rate between congenics and background strains, although a modest sex effect was found, with the females eliminating ethanol more rapidly than the males. We were unable to replicate previous differences found in LDA for the congenic on the ISS background, because none of the congenics differed from controls for LDA. congenics showed a differential effect of pentobarbital-induced LORR in the expected directions. The congenics on the ISS background showed more ethanol-induced ataxia than the ISS controls. Additionally, the hypothermic response seems affected by and and maybe others.


CONCLUSIONS
At least two regions carrying a QTL specifying sensitivity to high doses of ethanol cospecify altered sensitivity in other measures of alcohol action. Specifically, these QTLs clearly affect ethanol-induced hypothermia and pentobarbital-induced LORR and possibly ethanol-induced ataxia.
Owens
Jeremy C
JC
Institute for Behavioral Genetics, and the Department of Psychology, University of Colorado, Boulder, Colorado 80309-0447, USA.
Bennett
Beth
B
Johnson
Thomas E
TE
D000437:Alcoholism / Q000235:genetics*; D000818:Animals; D001259:Ataxia / Q000139:chemically induced / Q000235:genetics; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007035:Hypothermia / Q000139:chemically induced / Q000235:genetics; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D040641:Quantitative Trait Loci / Q000235:genetics*; D013045:Species Specificity
D006993:Hypnotics and Sedatives; D000431:Ethanol