Brain synaptosomal (Na+ and K+)ATPase activity as an index of tolerance to ethanol

Variations of brain synaptosomal (Na+ and K+)ATPase activity and development of functional tolerance to ethanol were followed simultaneously throughout a chronic ethanol treatment. Inhibition of the enzyme activity by ethanol added in vitro in the presence of noradrenaline was also assayed. Adult male rats were rendered tolerant to ethanol by daily intragastric administration of doses of 3-6 g of ethanol/kg body wt. As assessed by the hypothermic effect and impairment of motor performance on a tilting plane after injection of a challenge dose of ethanol (3 g/kg body wt. IP), functional tolerance developed slowly, was demonstrable after 2 weeks of treatment and increased for up to 4 weeks. The two tolerance tests gave parallel and positively correlated results. Concurrently with the development of tolerance, the basal activity of brain synaptosomal (Na+ and K+)ATPase increased (7% to 18%) in preparations from ethanol treated animals when compared to those from starch-fed caloric controls, and there was less inhibition of the enzyme by ethanol added in vitro in the presence of noradrenaline. The time course of the appearance of these changes in enzyme activity were positively correlated with that of behavioral tolerance, strengthening a relationship between the phenomena events. The intensity of the noradrenaline-ethanol interaction with the membrane-bound (Na+ and K+)ATPase activity could be an index of the degree of tolerance to ethanol.