Genetically determined differences in ethanol sensitivity influenced by body temperature during intoxication.
The present study investigated the importance of body temperature during intoxication in mediating differences between five inbred strains of mice (C57BL/6J; BALB/cJ; DBA/2J; A/HeJ; 129/J) in their acute sensitivity to the hypnotic effects of ethanol. Mice exposed to 22 degrees C after ethanol injection became hypothermic and exhibited statistically significant differences between strains in rectal temperatures at the return of the righting reflex (RORR), duration of loss of the righting reflex (LORR), and blood and brain ethanol concentrations at RORR. Exposure to 34 degrees C after injection offset ethanol-hypothermia and markedly reduced strain-related differences in rectal temperatures and blood and brain ethanol concentrations at RORR. Brain ethanol concentrations at RORR were significantly lower in C57, BALB, DBA and A/He mice exposed to 34 degrees C compared to mice exposed to 22 degrees C during intoxication suggesting that offsetting hypothermia increased ethanol sensitivity in these strains. Taken with previous in vitro studies, these results suggest that genetically determined differences in acute sensitivity to the behavioral effects of ethanol reflect differences in body temperature during intoxication as well as differences in sensitivity to the initial actions of ethanol at the cellular level.
Alkana
R L
RL
Institute for Toxicology, School of Pharmacy, University of Southern California, Los Angeles 90033.
Finn
D A
DA
Bejanian
M
M
Crabbe
J C
JC
D000064:Acclimatization; D000435:Alcoholic Intoxication / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D001831:Body Temperature; D001921:Brain / Q000378:metabolism; D003080:Cold Temperature; D000431:Ethanol / Q000493:pharmacokinetics; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*; D009043:Motor Activity; D012016:Reference Values; D012018:Reflex; D013045:Species Specificity
D000431:Ethanol