Measuring and Modifying Ethanol's Reinforcing Effects

测量和修改乙醇的增强效果

• 批准号: 6744146
• 负责人: GAIL D WINGER
• 金额: $ 50.51万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6744146
• 关键词: Macaca mulatta; acamprosate; alcoholic beverage consumption; behavioral /social science research tag; cocaine; diazepam; drug interactions; ethanol; fentanyl; gamma hydroxybutyrate; intravenous administration; naltrexone; psychometrics; psychopharmacology; reinforcer; self medication; substance abuse related behavior

DESCRIPTION (provided by applicant): In rhesus monkeys, the reinforcing effects of intravenously delivered ethanol lead to high ethanol intake, high ethanol blood levels, marked intoxication, and, under continuous access conditions, "binge" patterns of ethanol consumption, physiological dependence, and withdrawal signs. These are some of the characteristics of severe human alcoholism, a condition that is likely to result, at least in part, from this pharmacologically based reinforcing effect of ethanol. We suggest that response-contingent delivery of i.v. ethanol is a fairly "pure" measure of these reinforcing effects of ethanol, relatively unmodified by the aspects of taste, fluid volume, and gastrointestinal absorption that appear to prevent consumption by monkeys of equally large amounts of ethanol by the oral route. We propose to use behavioral economic procedures (demand curves) to quantify these reinforcing effects of i.v. ethanol and to compare them with those of other intravenously delivered drugs. In further studies, these procedures will be used to determine how the combination of ethanol and other drugs of abuse changes the reinforcing effects of both drugs. Because demand functions are unaltered by changes in drug potency, but are modified by changes in drug effectiveness, the measurements should indicate whether the various drug combinations result in a greater reinforcing effectiveness than either drug alone, or whether the potencies of the drugs as reinforcers are enhanced when they are combined. Finally, this same analysis will be used to determine how the treatment drugs of naltrexone and acamprosate modify the reinforcing effects of intravenous ethanol, again either by decreasing its reinforcing effectiveness or by decreasing its potency as a reinforcer. These studies will provide information not currently available on how ethanol compares with other drugs in terms of its reinforcing effectiveness, information that could impact policy decisions regarding legalization or decriminalization of other drugs of abuse. Data relevant to the behavioral and pharmacological mechanisms underlying polydrug abuse involving ethanol, and underlying pharmacological treatment of alcoholism will also be obtained.

描述（由申请人提供）：在恒河猴中，静脉内递送的乙醇的增强作用导致乙醇摄入量高，乙醇血液水平高，明显的中毒，在连续的接近条件下，“暴饮暴食”的“暴饮暴食”模式，乙醇消耗，生理依赖性，生理依赖性，生理依赖，，和提取标志。这些是严重的人类酒精中毒的某些特征，这种疾病至少部分是由于这种基于药理的乙醇增强作用而产生的。我们建议静脉注射的响应传递。乙醇是对乙醇的这些增强作用的一种相当“纯”的量度，该乙醇相对被味道，液体体积和胃肠道吸收的方面相对不适，这些乙醇似乎可以阻止口腔途径相同大量乙醇的猴子消耗。我们建议使用行为经济程序（需求曲线）来量化静脉注射的这些增强作用。乙醇并将其与其他静脉注射药物的乙醇进行比较。在进一步的研究中，这些程序将用于确定乙醇和其他滥用药物的组合如何改变两种药物的增强作用。由于需求功能因药物效力的变化而无法改变，但被药物有效性的变化所修改，因此测量值应表明各种药物组合是否比单独的药物产生更大的增强效率，还是药物的强度，还是药物作为增强剂的功能当它们合并时增强。最后，将使用相同的分析来确定纳曲酮的治疗药物和副盐如何通过降低其增强有效性或通过降低其作为增强剂的效力来改变静脉乙醇的增强作用。这些研究将提供有关乙醇在增强效率方面与其他药物进行比较的信息，这些信息可能会影响有关其他滥用药物的合法化或非刑事化的政策决策的信息。还将获得与涉及乙醇的多药滥用以及对酒精中毒的基础药理治疗相关的行为和药理机制有关的数据。