Models for examining selective effects of pharmacotherapy on reinforced behaviors

描述(由申请人提供)：改变乙醇维持行为的程度大于替代增强剂维持的行为的药物被认为是选择性的。这种选择性药物被认为是针对参与酒精强化的神经生物系统，并可能预测酗酒者的临床疗效。然而，这种选择性作用可能更多地依赖于强化的时间表，而不是药物对乙醇强化本身的任何直接的药理作用。阿卡米松、纳曲酮和恩丹西酮在动物研究中选择性地减少乙醇强化的几种措施，并为酗酒者提供长期益处。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影响，将评估对乙醇自我给药的选择性效应的一般性。每种药物(以ED50表示)对食物或乙醇的反应的效果将根据应答率、加强诊断率和背景(独立或同时获得)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影响的报道。结果将提供有关乙醇自我给药治疗的选择性效果是否可以预测临床疗效的信息。此外，结果将解决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影响的其他决定因素，如基线应答率、增强率或乙醇可获得性的背景。(相关性)通过测试不同的药物如何改变动物为酒精工作的方式，科学家可以更好地了解酒精在大脑中的工作方式，并开发更好的酒精中毒治疗方法。然而，为这类实验选择的环境对这些结果的影响程度仍然鲜为人知。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，这三种方法似乎也可以减少动物在不同条件下工作和饮酒的量。该项目将阐明酒精影响研究中的重要因素，以及对酗酒者的潜在药物治疗。

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.