Studies were conducted to determine if an animal has to experience a reduction in body temperature during the acquisition period in order to develop tolerance to the hypothermic effect of
ethanol. Adult,
drug-naive C57BL/6J mice were injected with 2.6 or 3.6 g/kg
ethanol or
normal saline once daily for 6 days. During the tolerance acquisition period, days 1-5, mice were placed into warmed chambers (36 +/- 2(0)C) which offset
ethanol hypothermia or into chambers at room temperature (24 +/- 1(0)C). On day 6, all mice were injected with
ethanol and placed into chambers at room temperature. Tolerance to
ethanol's hypothermic effect did not develop in the
ethanol-warm acquisition group. These mice had a significantly greater degree of
hypothermia on test day than the
ethanol-room temperature acquisition group, which showed tolerance, and their degree of hypothermic response was similar to that of mice injected with saline during acquisition. The differences between groups cannot be attributed to pharmacokinetic alterations or to conditioned responses since there were no differences between groups in blood or brain
ethanol concentrations on test day and all groups were exposed to the same acquisition and test situations. These results extend previous work to suggest that the development of tolerance to the physiological, as well as behavioral, aspects of
ethanol intoxication requires more than simple exposure to
ethanol.