Effects of chronic ethanol administration in the rat: relative dependency on dietary lipids--III. In vivo tolerance to hexobarbital.

Abstract Chronic administration of ethanol with either a high-fat (35% cal., including 2% cal. as linoleate) or a low-fat (2% cal. as linoleate) diet reduces similarly the hexobarbital sleeping times in the rat. Ethanol decreased the plasma and total body half-lives of hexobarbital in both dietary models, but they were decreased significantly more with the high-fat diet. A good correlation between hexobarbital plasma half-life and sleeping time was found only with the high-fat dietary model; the sleeping time was not a good index of hexobarbital metabolism in the low-fat model. Ethanol-fed rats awaken with significantly higher hexobarbital concentrations in brain and other tissues; this phenomenon is significantly more important in the high-fat model. Ethanol, administered chronically in nutritionally adequate liquid diets, increases tolerance to hexobarbital by increasing drug disposition and by decreasing central nervous system sensitivity. Both factors in tolerance are altered by modifications of the dietary lipid intake.