Rapidly developing functional tolerance to ethanol is accompanied by increased erythrocyte cholesterol in mice

We investigated the time course for development of functional tolerance to the ataxic effects of ethanol in four genetically distinct mouse populations. Two inbred-strains (C57BL/6J and DBA/2J) and two lines of mice (long-sleep and short-sleep) selectively bred for differences in acute ethanol sensitivity were used. Mice were injected i.p. with ethanol in doses that produced ataxia and were tested repeatedly for their ability to balance on a wooden rod. When they regained their balance at threshold, brain ethanol levels were measured in some mice and booster injections of ethanol were administered to the remaining animals. This sequence was repeated for five injections, delivering a total of 6 g/kg of ethanol to the final group of animals. Functional tolerance developed in all four populations of mice as evidence by threshold brain ethanol levels that were significantly higher after two or three successive injections than after one injection. The magnitude of tolerance was not increased by practice on the dowel. To investigate whether alterations in membrane lipid composition accompanied this rapid development of tolerance, we used erythrocytes as a model system and measured the cholesterol and phospholipid content of their membranes. The erythrocyte membranes from ethanol-tolerant mice of each population contained more cholesterol than those from controls. The erythrocyte membrane phospholipid content of ethanol-tolerant animals changed only slightly in two populations.