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Opioids: Relative Reinforcing Strength and Dependence

阿片类药物：相对强化强度和依赖性

基本信息

批准号：
7390859
负责人：
CAROL A PARONIS
金额：
$ 29.92万
依托单位：
MCLEAN HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-05-14 至 2010-03-31
项目状态：
已结题

项目摘要

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）：为了理解阿片类药物依赖的生理和行为方面已经付出了相当大的努力，但关于阿片类药物依赖如何改变海洛因的增强作用却知之甚少。自 1968 年首次证明动物无需事先依赖药物即可自行服用滥用药物以来，很少有研究检查阿片类药物依赖受试者的自我服用行为。拟议的研究旨在解决阿片类药物的增强作用是否以及如何随着依赖而改变的问题，包括因海洛因成瘾的已确定药物疗法（例如丁丙诺啡）而产生的依赖。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完整剂量效应函数。在这些新颖的选择程序中，受试者学习根据可用于自我注射和替代强化剂（食物）的静脉注射溶液的相对强化强特征来在整个过程中分配他们的行为。这些程序专门设计用于将药物的增强作用与其他行为影响分开。在拟议的研究中，海洛因和其他阿片类激动剂的自我给药将在不同的反应成本条件下确定，以评估背景对相对强化强度的影响。接下来，将进行研究以确定如何通过吗啡类药物的急性治疗和慢性治疗来调节海洛因的相对增强强度。初步数据表明，非依赖性受试者中海洛因的增强强度可以通过其他阿片类药物治疗或响应成本的变化而发生可预测的改变，证实了这些程序对于研究自我施用海洛因的相对增强强度的效用。这些研究完成后，将根据长期治疗过程中产生的耐受性和依赖性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影响。这些研究旨在凭经验解决阿片类药物成瘾人群滥用苯二氮卓类药物比例较高所引发的问题。总体而言，拟议的研究将为评估非依赖和阿片类药物依赖个体中海洛因增强强度的背景或药理学改变提供重大进展。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。