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Alcohol and Alcoholism Vol. 35, No. 5, pp. 435-438, 2000
© 2000 Medical Council on Alcoholism

PARADIGM TO TEST A DRUG-INDUCED AVERSION TO ETHANOL

E. Garver1, A. D. Ross2, G.-C. Tu1, Q.-N. Cao1, F. Zhou1 and Y. Israel1,3,*

1 Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107,
2 Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206, USA and
3 Center for Gene Pharmacotherapy, Millennium Institute, University of Chile, Santiago, Chile

Received 17 January 2000; in revised form 19 April 2000; accepted 5 May 2000

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 µM and 40–50 µM 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.


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