DRUG EFFECTS ON ALCOHOL REINFORCEMENT

减少酒精摄入的药物治疗效果

The efficacy of pharmacological therapies for reducing alcohol intake will be evaluated using a nonhuman primate model of alcohol-maintained responding. Ondansetron, a 5-HT3 receptor antagonist, and the opioid receptor antagonist naltrexone will be tested. Rhesus monkeys will be trained to orally self-administer alcohol during daily 3-hr operant conditioning sessions in which two different liquids will be available from two liquid delivery systems. For one series of experiments, alcohol and water will be concurrently available under independent fixed-ratio schedules of reinforcement. The effect of injections of the pretreatment drugs on subsequent alcohol-maintained responding will be measured and the following parameters will be manipulated: 1. frequency of pretreatment (acute versus chronic), 2. dose of the pretreatment drugs, and 3. dose (concentration) of the available alcohol solution. Of interest will be whether the drug pretreatments produce orderly and systematic shifts in the alcohol dose-response curve. For a second set of experiments, the effects of the drug pretreatments will be examined on responding maintained by an alcohol solution and a saccharin solution that is equally preferred to the alcohol solution. Two of the following: alcohol, saccharin solution, and/or water, will be available under a signalled fixed-interval schedule with mutually exclusive choice under each of the following conditions: 1. with alcohol and saccharin concurrently available throughout the daily sessions, and 2. with alcohol and saccarhin available sequentially within each daily session. This series will evaluate whether the drug pretreatments alter the reinforcing effects of alcohol in a manner that is specific to alcohol and not due to motor impairment and/or nonspecific decreases in all reinforced behavior. The use of a nonhuman primate model will allow the examination of a species that is physiologically and genetically more similar to humans than rodents, and allow the use of more sophisticated and longer term studies than are possible with rodents. In addition to testing the specific drugs proposed, the studies will lead to the development of valid and reliable procedures for testing other agents in the future.