Opioids:Relative Reinforcing Strength and Dependence

阿片类药物：相对强化强度和依赖性

• 批准号: 6895103
• 负责人: CAROL A PARONIS
• 金额: $ 32.2万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-14 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6895103
• 关键词: Macaca mulatta; behavioral /social science research tag; benzodiazepines; buprenorphine; disease /therapy duration; dosage; drug abuse chemotherapy; drug addiction; drug habituation; drug tolerance; gamma aminobutyrate; heroin; intravenous administration; intravenous drug abuse; narcotic antagonists; neurotransmitter agonist; opiate alkaloid; psychopharmacology; reinforcer; self medication; substance abuse related behavior

DESCRIPTION (provided by applicant): Considerable effort has been dedicated to understanding physiological and behavioral aspects of opioid dependence, yet little is known regarding how opioid dependence alters the reinforcing effects of heroin. Since 1968, when it was first demonstrated that prior dependence is not required for animals to initiate self-administration of abused drugs, very few studies have examined self-administration behavior in opioid-dependent subjects. The proposed research is designed to address questions of whether and how reinforcing effects of opioids are altered as a function of dependence, including dependence that results from identified pharmacotherapies for heroin addiction, e.g., buprenorphine. We have developed innovative self-administration procedures in which full dose-effect functions for the relative reinforcing strength of IV heroin can be rapidly determined. In these novel choice procedures, subjects learn to distribute their behavior throughout the session on the basis of the relative reinforcing strong features of an IV solution that is available for self-injection and an alternative reinforcer (food). These procedures are especially designed to divorce the reinforcing strength of drugs from other behavioral effects. In proposed studies, the self-administration of heroin and other opioid agonists will be determined under varying conditions of response cost to evaluate contextual influences on relative reinforcing strength. Next, studies will be conducted to determine how the relative reinforcing strength of heroin is modulated by acute treatment and chronic treatment with morphine-like drugs. Preliminary data indicate that the reinforcing strength of heroin in nondependent subjects can be predictably altered by treatment with other opioids or by changes in response cost, confirming the utility of these procedures for studies of the relative reinforcing strength of self-administered heroin. Following completion of these studies, alteration in the reinforcing strength of heroin will be gauged in relation to aspects of tolerance and dependence that develop during chronic treatment. Lastly, planned experiments will address the modification of heroin's reinforcing effects by nonopioid drugs, specifically GABA-A agonists. These studies are designed to empirically address questions raised by high rates of benzodiazepine abuse by opioid-addicted populations. Overall, the proposed studies will provide significant advances for evaluating contextual or pharmacological modifications of the reinforcing strength of heroin in nondependent and opioid-dependent individuals. Results of these studies will improve our ability to assess the effectiveness with which agonist-based medications may combat its addictive power.

描述(申请人提供)：已致力于了解阿片类药物依赖的生理和行为方面的相当大的努力，但关于阿片类药物依赖如何改变海洛因的强化效应知之甚少。自从1968年首次证明动物不需要事先依赖就能启动滥用药物的自我给药以来，很少有研究考察阿片类药物依赖受试者的自我给药行为。拟议的研究旨在解决以下问题：阿片类药物的增强效应是否以及如何作为依赖的函数而改变，包括因已确定的海洛因成瘾药物疗法(如丁丙诺啡)而导致的依赖。我们开发了创新的自我给药程序，可以快速确定静脉注射海洛因相对增强强度的全部剂量-效应函数。在这些新颖的选择程序中，受试者学习在整个过程中根据可供自我注射的静脉注射溶液和替代增强剂(食物)的相对强化的强大特征来分配他们的行为。这些程序是专门设计的，目的是将药物的强化作用与其他行为影响分开。在拟议的研究中，将在不同的反应成本条件下确定海洛因和其他阿片类激动剂的自我给药，以评估环境对相对强化强度的影响。下一步，将进行研究，以确定海洛因的相对增强强度是如何通过使用类吗啡药物的急性治疗和慢性治疗来调节的。初步数据表明，海洛因在非依赖者中的增强强度可以通过其他阿片类药物的治疗或反应成本的变化来预测地改变，证实了这些程序在研究自我给药海洛因的相对增强强度方面的有效性。在这些研究完成后，将根据长期治疗期间形成的耐受性和依赖性方面的变化来衡量海洛因增强强度的变化。最后，计划中的实验将解决非阿片类药物，特别是GABA-A激动剂对海洛因增强作用的修改。这些研究旨在经验性地解决阿片成瘾人群滥用苯二氮卓类药物的高比率所提出的问题。总体而言，拟议的研究将为评估海洛因在非依赖者和阿片依赖者中的增强强度的上下文或药理学修改提供重大进展。这些研究的结果将提高我们评估激动剂类药物对抗其成瘾能力的有效性的能力。