Paradigm to test a drug-induced aversion to ethanol.

The screening of new agents for aversive therapy of alcoholism requires a simple animal model. Animals trained to ingest ethanol solutions and subsequently administered a drug known to produce an aversion to ethanol in humans, do not readily make the association between the malaise induced by the aversive drug-ethanol reaction and the consumption of the same ethanol-containing solution that has been consumed previously without ill effects. An experimental paradigm is reported in which the malaise of the drug-ethanol reaction is quickly recognized by rats as derived from ethanol. Disulfiram was used as the model drug. Lewis rats were deprived of water for 18 h after which 6% (v/v) ethanol was offered as the only fluid. During the first hour of ethanol access, both controls (vehicle) and disulfiram (100 mg/kg)-treated animals consumed intoxicating amounts of ethanol (0.7-0.9 g ethanol/kg). Plasma acetaldehyde levels developed were 3-5 microM and 40-50 microM in the two groups respectively. After this time, disulfiram-treated animals virtually ceased consuming alcohol (90% inhibition), indicating that the disulfiram-ethanol reaction is associated with alcohol ingestion. Control animals continued consuming the alcohol solution for the additional 4-5 h tested. This model should be of value in the testing of new agents that reduce aldehyde dehydrogenase levels for prolonged periods for their potential as an aversive treatment in alcoholism.