Effect of treatment dose and test system on the development of ethanol tolerance and physical dependence.

The development of ethanol tolerance as a function of daily treatment dosage was examined on two different test systems. Tolerance to the motor-impairment effect of ethanol, as measured by the tilting-plane test, failed to develop after daily administration of 1-3 g/kg, but developed to equal degrees after 4 or 5 g/kg daily. On the other hand, daily treatment with 2, 4 or 6 g/kg all produced significant tolerance to the hypothermic effect, and the extent of tolerance was proportional to the treatment dosage. Twenty-four hours after the termination of ethanol treatment, there was a significant hypothermia in the group treated with 6 g/kg, and at 32 hr hyperthermia occurred in both the 4 and 6 g/kg groups. These results indicate that treatment dosage is an important determinant of the extent of ethanol tolerance and physical dependence, but that the relationship is complex and varies with the test system used.