Effect of 3-amino-1,2,4-triazole on the hypothermic effect of ethanol and on ethanol tolerance development.

The effect of aminotriazole (AT), inhibitor of catalase activity, on hypothermia and narcosis induced by ethanol and on the acquisition of tolerance to the ethanol hypothermic and narcotic effect was studied. Rats were pretreated with AT (1 g/kg IP) 1 hour before the test dose of ethanol (2.76 g/kg IP) and narcosis time, hypothermia and ethanol blood levels evaluated (first test). For studies on tolerance to ethanol, rats of the first test received daily (for 7 days) a dose of AT (1 g/kg IP) 1 hour before ethanol (2.76 g/kg) given by gavage, and the same parameters evaluated (8th day test). Results were compared to similar groups of rats without AT pretreatment (controls, 1st and 8th day test). Rats pretreated with AT exhibited a shorter narcosis time induced by ethanol but this treatment did not alter the hypothermic effect of ethanol nor ethanol disposal rate. Chronic ethanol treatment induced tolerance to the narcotic and hypothermic effect of ethanol as well as a metabolic tolerance. AT administered daily before the dose of ethanol produced a partial blockade of the development of tolerance to the narcotic effect of ethanol, but did not alter the development of hypothermic or metabolic tolerance. The brain catalase system seems to play a role in narcosis and on the development of tolerance to this effect of ethanol, but not in the hypothermic effect or in the development of tolerance to this ethanol effect. Since the inhibition of liver catalase activity by AT treatment was not correlated with changes in ethanol disposal rate, the liver catalase system appears not to play a role in the metabolic tolerance.