Involvement of brain ethanol metabolism on acute tolerance development and on ethanol consumption in alcohol-drinker...

Acute tolerance that develops in minutes of an ethanol exposure appears to influence voluntary ethanol consumption in our two selected bred lines, UChA (low ethanol drinker) and UChB (high ethanol drinker)rats. We have reported previously that an acute intraperitoneal (ip.) dose of ethanol (2.3 g/kg) induces both an increase in acute tolerance and a long-lasting increase in voluntary ethanol consumption in UChB rats. In the present paper we investigated the involvement of acetaldehyde produced centrally during ethanol oxidation by brain catalase and its oxidation by mitochondrial aldehyde dehydrogenase, on acute tolerance development and on voluntary ethanol consumption by rats. Acute tolerance developed to motor impairment induced by a dose of ethanol of 2.3 g/kg administered ip. was evaluated by the tilting plane test. Voluntary ethanol consumption by the rat with free access to a 10% v/v ethanol was measured daily. Both parameters were evaluated in controls,saline-pretreated and ethanol-injected rats. One group of rats that received the ethanol injection was pretreated with 3-amino-1,2,4-triazole (AT), a catalase inhibitor, and another group was pretreated with disulfiram, an aldehyde dehydrogenase inhibitor. Brain catalase and aldehyde dehydrogenase activities were measured in both groups of rats. Results show that acute tolerance to motor impairment, as well as ethanol consumption induced by ethanol, appears to be the consequence of acetaldehyde formed centrally during ethanol oxidation via the catalase system, because pretreatment of rats with the catalase inhibitor attenuated the increase in acute tolerance development and the increase in voluntary ethanol consumption in UChB rats that received the acute i.p. dose of ethanol. Moreover, the acetaldehyde metabolizing enzyme also appears to be an important factor in the modulation of acute tolerance development and voluntary ethanol consumption in UChA and UChB rats. The results lead us to propose that the possible mechanism by which the ip. injection of ethanol to UChB rats induces an increase in ethanol consumption is the development of acute tolerance, where acetaldehyde formed during brain ethanol metabolism via catalase and its subsequent oxidation via aldehyde dehydrogenase have an important role.