Models for examining selective effects of pharmacotherapy on reinforced behaviors

描述（由申请人提供）：药物在更大程度上改变由乙醇维持的行为，而不是由替代强化剂维持的行为，被认为是选择性的。这些选择性药物被认为是针对参与乙醇强化的神经生物学系统，并可能预测酗酒者的临床疗效。然而，这种选择性效应可能更多地取决于强化的时间表，而不是药物对乙醇强化本身的任何直接药理作用。在动物实验中，阿坎普罗酸、纳曲酮和昂丹司琼选择性地减少了几种乙醇强化措施，并为酗酒者提供了长期的益处。通过测试每种药物在几种不同强化方案下对乙醇和食物维持行为的急性效应，将评估对乙醇自我给药的选择性效应的普遍性。每种药物（ED50表达）对食物或乙醇反应的影响将根据反应率、强化率和环境（独立或并发获取）进行评估。这些实验将有助于我们解释选择性药物治疗对乙醇自我给药的影响。结果将提供关于乙醇自我给药的选择性治疗是否能预测临床疗效的信息。此外，研究结果将说明这种选择性效应是由于治疗的药理学，还是由于药物对行为的影响的其他决定因素，如基线反应率、强化率或乙醇可用性环境。通过测试不同的药物如何改变动物对酒精的工作方式，科学家们可以更好地了解酒精在大脑中的作用，并开发出更好的治疗酒精中毒的方法。然而，为这些实验选择的环境对这些结果的影响程度仍然知之甚少。这个项目将使用几个特别敏感的程序来研究三种有希望的酒精中毒治疗方法的效果，这些治疗方法似乎也减少了动物在不同条件下工作和饮酒的酒精量。该项目将澄清酒精影响研究和潜在的酗酒药物研究中涉及的重要因素。

DESCRIPTION (provided by applicant): Drugs that alter behaviors maintained by ethanol to a greater extent than behaviors maintained by an alternative reinforcer are considered selective. Such selective drugs are thought to target neurobiological systems involved in ethanol reinforcement and may prdict clinical efficacy in alcoholics. However, such selective effects may instead depend more on the schedule of reinforcement than on any direct, pharmacological effect of the drug on ethanol reinforcement per se. Acamprosate, naltrexone, and ondansetron selectively reduce several measures of ethanol reinforcement in animal studies and provide long-term benefits to alcoholics. By testing the acute effects of each drug on ethanol and food maintained behaviors under several different schedules of reinforcement, the generality of selective effects on ethanol self-administration will be assessed. Effects of each drug (expressed in ED50) on responding for either food or ethanol will be assessed in terms of response rate, reinforcerment rate, and context (independent or concurrent access). These experiments will aid our interpretation of reports of selective drug treatment effects on ethanol self- administration. Results will provide information about whether selective effects of treatments on ethanol self-administration are predictive of clinical efficacy. Further, results will address whether such selective effects are due to the pharmacology of the treatments or are due to other determinants of drug effects on behavior such as baseline response rate, reinforcement rate, or context of ethanol availability. (Relevance) By testing how different drugs alter the way animals work for alcohol, scientists can better understand how alcohol works in the brain and develop better treatments for alcoholism. Yet, the degree to which the circumstances chosen for such experiments impact these results is still poorly understood. This project will use several particularly sensitive procedures to study the effects of three promising treatments for alcoholism that also seems to decrease the amount of alcohol animals work for and drink under different conditions. This project will clarify important factors involved in studies of alcohol effects and potential medications for alcoholics.