ETHANOL TOLERANCE IN A GENETICALLY INSENSITIVE SELECTED MOUSE LINE

Mouse lines genetically susceptible (COLD) or resistant (HOT) to the acute hypothermic effects of ethanol were previously shown to differ in tolerance development: HOT mice did not develop tolerance, while COLD mice did. The present experiment increased the thermal load on HOT and COLD mice by administering ethanol chronically at an ambient temperature of 4-degrees-C. Under these conditions, initial hypothermic responses were as large as 10-degrees-C. Both HOT and COLD mouse lines developed significant tolerance by the third daily injection. Tolerance was dose-dependent: significant tolerance was seen only at the higher doses. HOT and COLD mouse lines developed approximately equal degrees of tolerance. Results support the hypothesis of a role for functional demand in the development of tolerance.