Features of environment-dependent tolerance to ethanol.

Mice given multiple injections of ethanol in a standardized environment develop environment-dependent tolerance to the hypnotic and hypothermic effects of ethanol. These animals also demonstrate environment-dependent cross-tolerance to the hypnotic and hypothermic effects of pentobarbital. Examination of the levels of ethanol in the brain and blood at various times after injection of a test dose of ethanol, as well as the examination of the rate of disappearance of ethanol from the blood, indicated that environment-dependent tolerance could be explained by dispositional factors. On the other hand, mice rendered tolerant to ethanol by a liquid diet technique demonstrate tolerance that is not environment-dependent, and there is no alteration in ethanol levels in different environments for animals fed the liquid diet. When the animals in either paradigm are tested by injecting ethanol directly into the brain, tolerance is observed that is not dependent on the environment. Tolerance produced by these two different paradigms is apparently due to different adaptive strategies used by the animal. Environment-dependent tolerance is partially related to the ability of the animal to change the disposition of ethanol, while environment-independent tolerance may be entirely due to other factors, such as changes in neuronal sensitivity to ethanol.