DRUG EFFECTS ON ALCOHOL REINFORCEMENT

减少酒精摄入的药物治疗的有效性 将使用非人灵长类动物模型进行评估， 响应. 5-HT 3受体拮抗剂昂丹司琼与阿片类药物 将测试受体拮抗剂纳洛酮。恒河猴将会 接受过每日3小时操作期间口服自我给药酒精的培训 两种不同的液体将提供条件反射会议 两个液体输送系统。在一系列实验中，酒精 水将在独立的固定比例下同时提供 强化计划。预处理注射液的作用 将测量药物对后续酒精维持反应的影响， 将操纵以下参数：1.频率 预处理（急性与慢性），2.预处理药物的剂量， 和3.可用酒精溶液的剂量（浓度）。的 兴趣将是药物预处理是否产生有序， 酒精剂量反应曲线的系统性偏移。针对第二组 实验中，将检查药物预处理的效果 在由酒精溶液和糖精溶液维持的响应上， 其与醇溶液同样优选。以下两项： 酒精、糖精溶液和/或水，将在 具有互斥选择信号固定间隔调度 以下条件中的每一个：1.酒精和糖精 在整个日常会话中同时可用，以及2.用酒精 和saccarhin在每个每日疗程内顺序可用。这 系列将评估药物预处理是否改变了增强 以特定于酒精的方式影响酒精，而不是由于 运动障碍和/或非特异性减少，所有加强 行为使用非人类灵长类动物模型将允许检查 一个在生理和基因上与 人类比啮齿动物，并允许使用更复杂和更长的时间， 长期的研究比可能与啮齿动物。除了测试 具体的药物建议，研究将导致发展 今后测试其他制剂的有效和可靠的程序。

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.