Development of tolerance to the plasma amino acid-decreasing effect of ethanol in the rat.

Male Sprague-Dawley rats were treated for one month with daily intraperitoneal injections of ethanol (2 g kg-1), or saline. After this pretreatment, animals from each group were given acute doses of ethanol (2 g kg-1) or saline. Plasma amino acid concentrations and brain tyrosine, tryptophan, dopamine, 5-HT and 5-HIAA concentrations were measured in samples collected 1 h after the injections. Acute administration of ethanol induced a dramatic fall in the concentrations of 18 out of 20 plasma amino acids in animals pretreated with saline. In animals chronically pretreated with ethanol this decrease was much smaller. Furthermore, the decrease was significantly lower for 6 of the measured amino acids in the chronic ethanol group compared with the saline-treated control group. Tolerance to the plasma amino acid decreasing effect of ethanol had thus developed. This acquired tolerance might be explained by both pharmacokinetic and pharmacodynamic mechanisms. Chronic administration of ethanol induced increased concentrations of tyrosine and dopamine in the brain, probably due to increased transport of tyrosine into the brain caused by an increase in the ratio of tyrosine to large neutral amino acids in plasma.