Cellular and learned tolerances for ethanol hypothermia.

Four groups of rats received ethanol: 1) intermittently while experiencing hypothermia, 2) chronically while experiencing hypothermia, 3) intermittently while protected from hypothermia, and 4) chronically while being protected from hypothermia. On postchronic testing, Group 1 showed tolerance to 2.0 and 2.3 but not 2.7 g/kg ethanol, Group 2 was tolerant to all 3 doses, Group 3 was tolerant to none, and Group 4 was tolerant only to 2.7 g/kg. On withdrawal of chronic ethanol or vehicle, Groups 1 and 2 showed trends to lose tolerance which became significant after subsequent extinction training. The treatments were repeated in other rats up to the postchronic test for tolerance, after which they were killed at 15-120 min after ethanol to assay serum and brain concentrations. Serum and brain levels of ethanol were higher in Groups 2 and 4 despite less intense hypothermia (i.e., no metabolic tolerance). Analysis of covariance indicated less tolerance in Group 1 vs. Group 2 and Group 3 vs. Group 4 for the same brain levels of ethanol (i.e., cellular tolerance in Groups 2 and 4). Therefore, both learned and cellular tolerances were observed in these subjects and appeared to be separable phenomena according to the various treatments imposed.