DISCRIMINATION OF ABUSED DRUG MIXTURES

对滥用药物混合物的歧视

• 批准号: 2117823
• 负责人: IAN P STOLERMAN
• 金额: $ 10.65万
• 依托单位: UNIVERSITY OF LONDON INST OF PSYCHIATRY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-01 至 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2117823
• 关键词: amphetamines; behavior test; cyclazocine; discrimination learning; dopamine receptor; dosage; drug abuse; drug addiction antagonist; drug interactions; laboratory rat; learning; midazolam; operant conditionings; paired stimuli; pentobarbital; psychopharmacologic agent; psychopharmacology; sensory discrimination; serotonin; toxicology

The aims are firstly, to explore the characteristics of behavior based on the discriminative stimulus effects of drug mixtures and secondly, to investigate whether methods derived from work on mixtures can be applied to clarifying the mode of action of single drugs with multiple effects. Most drug discrimination studies focus almost exclusively on single drugs, whereas the abuse of mixtures of more than one drug at a time is a widespread health problem. Both mixtures of drugs and single drugs with multiple effects may be discriminated as a stimulus complex consisting of two or more elements and studies will clarify ways in which such compound, interoceptive stimuli are processed. The work will build upon knowledge gained in recent years from studies of the discriminative stimulus effects of mixtures and will emphasize mainly the effects of behavioral variables on the characteristics of such discriminations in rats. The influence of both the current conditions and of behavioral variables on the characteristics of such discriminations in rats. The influence of both the current conditions and of behavioral and pharmacological histories will be examined. The behavioral variables will include the alternative responses available in operant conditioning procedures for assessing discriminative effects and the consequences of devaluing the discriminative significance of stimulus elements by overshadowing, psychological blocking, and extinction procedures. The specificity of discriminative stimuli trained in different ways with mixtures of abused substances such as amphetamine and pentobarbital will be evaluated in generalization tests with pharmacologically similar drugs and drug mixtures, and with compounds from other pharmacological classes. Other studies will examine the role of a pharmacological variable, the time- course of drug action, in controlling overshadowing (which in turn contributes to the pharmacological characteristics of drug discriminations). The effects of a previous history of exposure to particular training conditions will be compared with the effects of drug exposure alone to elucidate the interacting roles of behavioral history and pharmacological history as determinants of discriminative responses to abused drug mixtures. Later studies will examine applications of the methods to single drugs with multiple effects; principles emerging from the previous and the future work on the project will be applied to the discrimination of the opioid cyclazocine and the hallucinogen lysergic acid diethylamide (LSD), each of which may bring about its effects through actions on more than one type of receptor. Novel drug discrimination procedures that have been developed in previous work on the project include ways of training discriminations that may enhance pharmacological specificity (the so-called AND-OR discrimination procedure). The practical value of these methods, and of cue manipulation by means of overshadowing, blocking and extinction procedures, will be assessed in experiments that will attempt to elucidate the role of kappa opioid and phencyclidine receptors in responses to cyclazocine, and of 5-HT/2 and dopamine receptors in responses to LSD. These experiments are, however, presented primarily as a way for developing novel methodologies that may be applicable to drugs from many classes, rather than as investigations in depth on cyclazocine and LSD.

目的首先是探索基于行为的特征 药物混合物的歧视性刺激作用，其次是 调查是否可以采用从混合物上的工作得出的方法 阐明具有多种作用的单一药物的作用方式。 大多数药物歧视研究几乎完全关注 药物，而一次滥用混合物一次以上药物是 广泛的健康问题。 药物的混合物和单一药物的混合物与 多种效果可能被区分为一个刺激复合物，由 两个或多个元素和研究将阐明这种化合物的方法， 处理性刺激被处理。 这项工作将基于知识 近年来，通过研究歧视性刺激效应而获得 混合物的主要强调行为变量的影响 关于大鼠这种歧视的特征。 影响 当前条件和行为变量 大鼠这种歧视的特征。 两者的影响 当前条件以及行为和药理历史 将被检查。 行为变量将包括替代方案 在操作调节程序中可用的响应用于评估 歧视效果和贬值的后果 刺激元素的歧视意义​​是通过遮盖的刺激元素 心理阻塞和灭绝程序。 特异性 通过滥用混合物以不同方式训练的歧视性刺激 将评估苯丙胺和戊巴比妥等物质 用药理学相似的药物和药物进行概括测试 混合物，以及其他药理类别的化合物。 其他 研究将检查药理学变量的作用，时间 - 毒品行动的过程，控制过度掩饰（反过来又 有助于药物的药理特征 歧视）。 先前接触历史的影响 将特定的培训条件与药物的影响进行比较 单独接触以阐明行为历史的相互作用 和药理学历史作为歧视性反应的决定因素 滥用的药物混合物。 后来的研究将检查 具有多种作用的单一药物的方法；从中出现的原则 该项目的上一项和未来工作将应用于 阿片类细胞cy虫和致幻蛋白菌丝的歧视 酸二乙酰胺（LSD），每种都可能通过 对多种受体的作用。 新型药物歧视 该项目先前工作中已经开发的程序 包括训练歧视的方法，可以增强药理 特异性（所谓的和或歧视程序）。 这 这些方法的实际价值，以及通过 将评估遮盖，阻塞和灭绝程序 试图阐明Kappa阿片类药物和的实验 苯基酮受体对环孢菌素的反应以及5-HT/2的反应 多巴胺受体对LSD的反应。 但是，这些实验是 主要是开发可能的新方法的一种方式 适用于许多班级的药物，而不是作为调查 气囊和LSD的深度。