Biochemical correlates of tolerance in rodents and in Drosophila. Possible role of alcohol dehydrogenase, aldehyde dehydrogenase and superoxide dismutase.

In the rat, prolonged exposure to ethanol (ETOH) vapor induced an acquired increase in tolerance. After a single ETOH administration, the duration of recovery was decreased by 20% as compared to control animals and the rate of ETOH elimination from blood was increased by 27%. From the data obtained on liver enzymes--alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH) and superoxide dismutase (SOD)--it is suggested that the increased ALDH activity would be the consequence of an increased formation of the product of ETOH oxidation, the acetaldehyde. This over-production would not be accounted for by ADH. It is assumed that among others, the coupled reaction SOD-catalase would represent a possible alternate pathway. Data on Drosophila demonstrate that initial tolerance to ETOH is well correlated with ADH activity. It is suggested that ETOH metabolites (mainly acetaldehyde) would act also as determinant of this initial tolerance. The value of Drosophila as animal model for the study of behavioral and biochemical correlates of initial tolerance is discussed.