Chronic functional ethanol tolerance in mice influenced by body temperature during acquisition

Previous studies have found that body temperature during intoxication influences brain sensitivity to ethanol with the sensitivity being less at cool than at warm body temperatures. If this effect of temperature reflects alterations in the acute membrane perturbing action of ethanol, as suggested by in vitro studies, then body temperature reduction (hypothermia) during tolerance acquisition should reduce the effectiveness of a given ethanol concentration and, in turn, should reduce the development of chronic functional ethanol tolerance. To test this hypothesis, adult drug-naive C57BL/6J mice were injected i.p. once daily for five days with 3.6 g/kg ethanol (20% w/v) and were exposed to 34°C or 25°C for five hours following injection. On day 6, both ethanol acquisition groups and naive mice were injected i.p. with 4.0 g/kg ethanol and exposed to 25°C. During acquisition, the group exposed to 34°C had significantly higher body temperatures than the mice exposed to 25°C, and there were no statistically significant differences in blood ethanol concentrations between treatment conditions. The extent of tolerance on day 6, measured by sleep-times and wake-up blood and brain ethanol concentrations versus naive mice, was significantly greater in the 34°C acquisition group than in the 25°C acquisition group. The results demonstrate that body temperature influences tolerance development in the manner predicted by membrane perturbation theories of anesthesia and adaptation based tolerance theories.