Opioids:Relative Reinforcing Strength and Dependence

阿片类药物：相对强化强度和依赖性

• 批准号: 7071165
• 负责人: CAROL A PARONIS
• 金额: $ 31.44万
• 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/7071165
• 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（由申请人提供）：相当大的努力一直致力于了解阿片类药物依赖的生理和行为方面，但很少有人知道阿片类药物依赖如何改变海洛因的强化作用。自1968年首次证明动物开始自我给药滥用药物不需要先前的依赖性以来，很少有研究检查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阿片类药物的强化作用是否以及如何作为依赖性的函数而改变的问题，包括由确定的海洛因成瘾药物治疗引起的依赖，例如，丁丙诺啡我们已经开发出创新的自我管理程序，其中充分的剂量效应功能的相对加强强度的IV海洛因可以迅速确定。在这些新的选择程序中，受试者学习在整个会话中基于可用于自我注射的IV溶液和替代替代替代品（食物）的相对强化的强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力量与其他行为效应分离开来。在拟议的研究中，海洛因和其他阿片类激动剂的自我管理将在不同的反应成本条件下确定，以评估相对强化强度的背景影响。接下来，将进行研究，以确定海洛因的相对强化强度如何通过吗啡类药物的急性治疗和慢性治疗来调节。初步数据表明，海洛因在非依赖性受试者中的强化强度可以通过其他阿片类药物治疗或响应成本的变化来预测改变，从而证实了这些程序对自我管理海洛因的相对强化强度研究的实用性。在完成这些研究之后，将根据长期治疗期间形成的耐受性和依赖性方面来衡量海洛因强化强度的变化。最后，计划中的实验将解决非阿片类药物，特别是GABA-A激动剂对海洛因强化作用的改变。这些研究的目的是从经验上解决阿片类成瘾人群苯二氮卓类药物滥用率高所提出的问题。总体而言，拟议的研究将提供显着的进步，评价上下文或药理学修改的增强强度的海洛因在非依赖和阿片类药物依赖的个人。这些研究的结果将提高我们评估基于激动剂的药物对抗其成瘾能力的有效性的能力。