DETERMINANTS OF THE BEHAVIORAL EFFECTS OF ABUSED DRUGS

滥用药物的行为影响已被证明取决于 生物体先前的行为经验，以及更直接的 行为特征及其控制环境。 实验 本提案中概述的这些行为原则 与选定的药物一起检查和澄清 行为和药理学机制的作用， 苯二氮卓类 松鼠猴的表现将被建立， 在响应生产食物或 电击演示 先前的研究表明， 苯二氮卓类药物通过增加 食物维持反应，减少或消除可比 通过电击维持反应。 惩罚和不惩罚 性能，也不同敏感的苯二氮卓类，将 也被雇用。 选定苯二氮卓类药物的剂量反应函数， 非苯并二氮卓类镇静催眠药如巴比妥类，和新的， 当使用时，将获得临床有效的化合物，例如丁螺环酮， 单独给药和在其它药剂存在下给药。 特别 感兴趣的是最近的苯并二氮杂受体拮抗剂，以及 化合物，如β-咔啉和嘌呤能药物， 显示出拮抗苯二氮卓类药物的作用或相互作用 与苯二氮卓类受体的联系 进一步的研究将探讨如何行为的影响， 苯并二氮杂卓类被具有相对特异性的其它化合物修饰， 对某些神经递质系统的影响 其中包括化合物 它们是γ-氨基丁酸、血清素 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情况 通过提供合适的行为史。 这些实验应该 在行为的综合水平上提供有价值的信息， 行为和药理学机制的活动， 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.