Sensitivity and tolerance to ethanol-induced hypothermia in genetically selected mice.
COLD mice have been genetically selected for pronounced hypothermia (HT) after acute EtOH administration, whereas HOT mice have been selected for attenuated HT. In the current experiments, HOT and COLD mice were found to differ significantly in sensitivity to EtOH-induced HT across a range of doses: the difference was greater at higher doses. After 3 g/kg of EtOH, HOT mice displayed a 1.8 degrees C HT, whereas COLD mice had a 3.6 degrees C HT. Male mice had greater HT responses than female mice regardless of genotype. Nonselected control mice were intermediate to the HOT and COLD mice in responsiveness to EtOH. After an acute EtOH dose, HOT mice were found to have slightly lower brain EtOH concentrations than COLD mice 3 and 4 (but not 1 and 2) hr after administration of EtOH, and may have eliminated EtOH slightly more rapidly than COLD mice. When tested repeatedly in a cool ambient environment (18 degrees C), COLD mice developed tolerance to EtOH hypothermia, whereas HOT mice did not. These results confirm that sensitivity to the hypothermic effects of EtOH is influenced markedly by genotype. Furthermore, selection for neurosensitivity to EtOH has produced a correlated difference in rate or magnitude of tolerance development, which is consistent with an hypothesis of the influence of common genes determining these responses to EtOH. The difference in tolerance could not be accounted for by initial HT sensitivity differences between the lines. The HOT and COLD lines should be useful for studies of the neurobiological mechanisms of EtOH-induced HT.(ABSTRACT TRUNCATED AT 250 WORDS)
Crabbe
J C
JC
Research Service, Veterans Administration Medical Center, Portland, Oregon.
Feller
D J
DJ
Dorow
J S
JS
D000704:Analysis of Variance; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D001833:Body Temperature Regulation; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D005838:Genotype; D008297:Male; D051379:Mice
D000431:Ethanol