Relationship between initial sensitivity, acute tolerance and chronic tolerance to ethanol in a heterogeneous population of Swiss mice.

Acute and chronic tolerance to ethanol hypothermia as a function of the initial sensitivity were examined in a heterogeneous population of Swiss mice. Based on their day 1 hypothermic response to a challenge dose of ethanol (4 g/kg, IP), 60 mice were divided into three groups: high responders (HR: delta Tmax 6.5-9 degrees C, n = 14); medium responders MR: delta Tmax 4.75-6.25 degrees C, n = 31); and low responders (LR: delta Tmax 3-4.5 degrees C, n = 15). Animals were injected once daily (between 9 and 11 A.M.) with 4 g/kg ethanol (20% w/v) for a period of 7 days. Testing was repeated on days 3 and 7 after the administration of the same dose of ethanol. The HR group showed the highest degree of chronic tolerance to ethanol hypothermia, followed by the MR group, while the LR group developed no chronic tolerance. Acute tolerance was considered to be present when delta T was lower at the same blood alcohol concentration (BAC), or BAC was higher at the same delta T, at later times in the same mouse. On days 3 and 7, the HR and MR showed acute tolerance, while the LR did not. Although metabolic tolerance to ethanol was detected in all three groups, ethanol metabolism played a minor role in initial sensitivity and acute and chronic ethanol tolerance.