DETERMINANTS OF THE BEHAVIORAL EFFECTS OF ABUSED DRUGS

滥用药物的行为影响已被证明依赖于 有机体先前的行为经验，以及更直接的 行为特征及其控制环境。实验 在本提案中概述的是旨在使用这些行为原则 与选定的药理药物一起检查和澄清 其作用的行为和药理学机制 苯二氮卓类。将建立松鼠猴子的表演和 根据程序维护，在该程序中，响应产生食物或 电击演示。此前的研究表明， 苯二氮卓类药物通过增加 食物维持的反应，减少或消除可比性 由电击维持的反应。受惩罚和不受惩罚 对苯二氮卓类药物也有不同敏感的表现，将 也会被雇佣。部分苯二氮卓类药物的剂量-反应函数， 非苯二氮卓类镇静催眠药，如巴比妥类，以及新奇的， 临床有效的化合物，如丁螺环酮，将在 单独给药和在其他代理人在场的情况下给药。特别的 令人感兴趣的是最近的苯二氮卓受体拮抗剂以及 化合物，如Beta-Carolines和嘌呤能药物，已经 显示出要么拮抗苯二氮卓类药物的作用，要么相互作用 与苯二氮卓类受体的作用方式尚不完全清楚。 进一步的研究将考察这些行为的影响 苯并二氮卓类药物被其他化合物修饰，这些化合物具有相对特异性 对某些神经递质系统的活动。其中包括化合物 它们是伽马氨基丁酸、5-羟色胺的激动剂和拮抗剂 和去甲肾上腺素能系统。这些研究将扩展到 苯二氮卓类药物的行为效应被逆转的条件 通过提供合适的行为史。这些实验应该 在行为的综合层面上提供有价值的信息 一种潜在的行为和药理学机制 滥用药物的主要类别。

The behavioral effects of abused drugs have been shown to depend on the organism's prior behavioral experience, as well as on the more immediate characteristics of behavior and its controlling environment. Experiments outlined in this proposal are designed to use these behavioral principles together with selected pharmacological agents to examine and clarify the behavioral and pharmacological mechanisms underlying the actions of the benzodiazepines. Performances of squirrel monkeys will be established and maintained under procedures in which responding produces either food or electric shock presentation. Previous research has shown that benzodiazepines differentially affect these behaviors by increasing food-maintained responding and either decreasing or eliminating comparable responding maintained by electric shock. Punished and unpunished performances, also differentially sensitive to the benzodiazepines, will also be employed. Dose-response functions for selected benzodiazepines, nonbenzodiazepine sedative-hypnotics such as the barbiturates, and novel, clinically-effective compounds such as buspirone, will be obtained when administered alone and in the presence of other agents. Of particular interest are the recent benzodiazepine receptor antagonists, as well as compounds such as the Beta-carbolines and purinergic drugs which have been shown to either antagonize the effects of the benzodiazepines or interact with the benzodiazepine receptor in as yet incompletely understood ways. Further studies will examine how the behavioral effects of the benzodiazepines are modified by other compounds with relatively specific activity on certain neurotransmitter systems. These include compounds which are agonists and antagonists of the gammaaminobutyric acid, serotonin and noradrenergic systems. These studies will then be extended to conditions where the behavioral effects of the benzodiazepines are reversed by providing a suitable behavioral history. These experiments should provide valuable information at the integrative level of behavior on the behavioral and pharmacological mechanisms underlying the activity of a major class of abused drugs.