DRUG EFFECTS ON ALCOHOL REINFORCEMENT

减少酒精摄入量的药物治疗效果 将使用酒精维持的非人类灵长类动物模型进行评估 正在回应。5-HT3受体拮抗剂恩丹西酮和阿片类药物 受体拮抗剂纳曲酮将接受测试。恒河猴将会是 接受培训，在每天3小时的手术中自行口服酒精 提供两种不同液体的调理课程 来自两个液体输送系统。在一系列实验中，酒精 在独立的固定比例下，水将同时可用 加固明细表。注射前处理的效果 随后将测量药物对酒精维持的反应，并 将操作以下参数：1.频率 前处理(急性和慢性)，2.前处理药物的剂量， 3.可用酒精溶液的剂量(浓度)。的 人们感兴趣的将是药物前处理是否有序和 酒精剂量-反应曲线的系统性变化。对于第二套 在实验中，将检验药物预处理的效果。 酒精溶液和糖精溶液维持反应的研究 与酒精溶液相比，这同样是首选的。以下两项： 酒精、糖精溶液和/或水将在 具有互斥选择的有信号的固定间隔调度 以下每一种情况：1.含酒精和糖精 在日常会话中同时可用，2.含酒精 和Saccarhin在每个日常会话中顺序可用。这 系列将评估药物预处理是否改变了增强 酒精以一种特定于酒精而非应有的方式产生的影响 所有增强的运动障碍和/或非特异性减少 行为。使用非人类灵长类动物模型将允许进行检查 指在生理和基因上更接近于 人类比啮齿动物，允许使用更复杂和更长的时间 对于啮齿动物来说，学期学习是不可能的。除了测试 具体药物的提出，研究将导致开发 为将来测试其他试剂提供有效和可靠的程序。

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.