MECHANISMS OF OPIATE AND STIMULANT DRUG REINFORCEMENT

阿片类药物和兴奋剂药物的强化机制

• 批准号: 6489461
• 负责人: AARON ETTENBERG
• 金额: $ 14.33万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-03-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6489461
• 关键词: anxiety; behavior test; behavioral extinction; behavioral habituation /sensitization; brain mapping; cocaine; diazepam; dopamine antagonists; drug metabolism; drug withdrawal; heroin; laboratory rat; motivation; operant conditionings; psychopharmacology; reinforcer; self medication; serotonin inhibitor; substance abuse related behavior; substance abuse related disorder

DESCRIPTION: (Applicant's Abstract) The primary long-term goal of this project is to employ behavioral pharmacological methods to investigate neura1 substrates underlying the self-administration of opiate and stimulant drugs of abuse. Toward this end, three specific aims are described each of which is intended to build upon and extend the work completed during the first nine years of this project. These are; 1) to continue investigations of the putative reward-attenuating actions of dopamine antagonist drugs on opiate- and stimulant-reinforced behaviors; 2) to further examine the role of drug-paired stimuli in drug self-administration and drug relapse; and 3) to continue investigations of the anxiogenic side effects of chronic cocaine. The hypothesis driving this work is that central dopaminergic (DA) systems are responsible for the reinforcing properties of both opiate and stimulant drugs. While this position is hardly unique, the methodological approach taken in this project is novel in a number of ways: I) while traditional lever-press procedures examine the behavior of drugged animals working to maintain their drug plasma levels, the current project examines IV drug reinforcement using an operant runway where animals received only one drug injection per day. In this context, the speed with which Ss traverse the alley for drug reinforcement has operationally provided a reliable index of the undrugged animals' motivation to obtain the reinforcer; ii) by testing only one trial per day, the resulting data are devoid of potential confounding and nonspecific effects produced by the drug reinforcers themselves; iii) a response reinstatement test is used to examine the factors that result in the reinstatement of operant runway behavior after a prolonged period of abstinence, and hence serves as a viable model of human drug relapse; and iv) in each of the studies, the putative reinforcement-attenuating actions of antagonist drugs are assessed at a time when the drug's direct pharmacological effects are no longer present (i.e., on the first post-treatment trial 24 hrs post-injection). This permits conclusions about antagonist effects on operant behavior that are not confounded by the sedative arrd motoric side-effects of these test agents. In summary, the work proposed in this application is intended to provide important new information about the nature and neurobiology of both the positive and negative factors that together determine the nature and extent of human drug self-administration behaviors.

描述：(申请人摘要) 该项目的主要长期目标是使用行为 药理学方法研究神经生长因子1的底物 自行管理鸦片类和兴奋剂类药物的滥用。朝向这个方向 最后，描述了三个具体目标，每个目标都旨在建立 在此基础上延长本年度头九年完成的工作 项目。这些是：1)继续调查推定的 多巴胺拮抗剂药物对阿片类药物的奖赏减弱作用 刺激剂强化的行为；2)进一步研究 药物自我给药与药物复吸中的药物配对刺激； 继续研究慢性可卡因引起焦虑的副作用。 推动这项工作的假设是中枢多巴胺(DA)系统 对阿片剂和兴奋剂的增强作用负责 毒品。虽然这一立场很难说是独一无二的，但方法论方法 这个项目在许多方面都是新颖的：i)虽然传统 杠杆按压程序检查被下药的动物的行为 维持他们的药物血浆水平，目前的项目检查IV药物 在动物只接受一种药物的情况下使用可操作的跑道进行增援 每天注射一次。在这种情况下，SS遍历 加强禁毒工作的胡同在业务上提供了一个可靠的指标 未下药的动物获得增强剂的动机；ii)通过测试 每天只有一次试验，结果数据是没有潜力的 药物增强剂产生的混杂和非特异性作用 Iii)使用响应恢复测试来检查 导致可操作跑道行为在一年后恢复的因素 长期禁欲，因此成为人类的一个活的模型 毒品复发；以及iv)在每项研究中，推定的 一次评估拮抗剂的增强-减弱作用 当药物的直接药理作用不再存在时(即， 在注射后24小时后的第一次试验中)。这允许 关于拮抗剂对操作者行为的影响的结论 被这些测试剂的镇静剂和运动性副作用搞混了。 总之，本申请中提议的工作旨在提供 关于两种病毒的性质和神经生物学的重要新信息 积极的和消极的因素共同决定了性质和程度 人类药物自我给药行为。