Paradigm to test a drug-induced aversion to ethanol

Garver, E Ross, AD Tu, GC Cao, QN Zhou, F Israel, Y

E. Garver et al., Paradigm to test a drug-induced aversion to ethanol, ALC ALCOHOL, 35(5), 2000, pp. 435-438

31

INGLESE

Article

Clinical Psycology & Psychiatry","Neurosciences & Behavoir

ALCOHOL AND ALCOHOLISM

0735-0414 → ACNP

35

5

2000

435 - 438

ISI

0735-0414(200009/10)35:5<435:PTTADA>2.0.ZU;2-E

The screening of new agents for aversive therapy of alcoholism requires a s imple animal model. Animals trained to ingest ethanol solutions and subsequ ently administered a drug known to produce an aversion to ethanol in humans , do not readily make the association between the malaise induced by the av ersive drug-ethanol reaction and the consumption of the same ethanol-contai ning solution that has been consumed previously without ill effects. An exp erimental paradigm is reported in which the malaise of the drug-ethanol rea ction 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 w hich 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)-treat ed animals consumed intoxicating amounts of ethanol (0.7-0.9 g ethanol/kg). Plasma acetaldehyde levels developed were 3-5 muM and 40-50 muM 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 cont inued 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 aversi ve treatment in alcoholism.