PSYCHOPHARMACOLOGY OF STIMULANTS AND OPIOID PEPTIDES

本申请描述了一项为期五年的研究计划， 兴奋剂和阿片类药物的精神药理学。 该研究将利用 许多不同的方法，包括行为。药理学上， 神经化学和电生理技术来进一步表征 这些物质的影响，并阐明其潜在的 行动机制。 根据详细的观察，我们发现 一般行为特征或维度（即，固执和 环境参与），区分响应曲线 与不同类型的兴奋剂有关， 物种差异。 我们已经制定了业务定义的措施， 这些行为维度， 研究旨在进一步完善这些措施，并测试我们的 关于潜在的单胺能系统和机制的假说。 的 我们提出的刺激反应的明显普遍特征， 在大鼠中进行研究可能与广泛的刺激作用有关 并涉及这些药剂在治疗 多动儿童 阿片类药物的急性和慢性行为激活作用将被 在大鼠中的特征和阿片受体介导的机制的作用 和单胺系统的基础上的各种响应组件将是 使用各种药理学、神经化学和 离散脑内注射技术。 类似的行为和 机制研究也计划比较和对比激活 推定的σ受体激动剂的作用（例如，SKF-10，047）和PCP， 吗啡样药物（μ受体激动剂）和阿片类药物产生的那些 缩氨酸 此外，还将进行一系列的实验， 研究内源性阿片系统在阿片样反应中的作用 与轻度应激相关的激活。 我们的研究涉及 阿片类药物诱导的刺激导向行为的改变也将被 持续期间内的 阿片类药物诱导的行为激活可能与 麻醉性欣快症和寻求药物的行为，此外， 一个适合各种精神病理学的动物行为模型 其中内源性阿片类药物已经被引入。

This application describes a five-year program of research to study the psychopharmacology of stimulants and opioids. The research will utilize a number of different methodologies including behavioral. pharmacological, neurochemical, and electrophysiological techniques to further characterize the effects of these substances and to elucidate their underlying mechanisms of action. Based on detailed observations, we have identified general behavioral features or dimensions (i.e., perseveration and environmental engagement) which distinguish the response profiles associated with different types of stimulants and which appear to transcend species differences. We have developed operationally defined measures of these behavioral dimensions that subsume a variety of specific responses and studies are designed to further refine these measures and to test our hypotheses regarding underlying monoaminergic systems and mechanisms. The apparently pervasive characteristics of the stimulant response we propo se to study in rats may be relevant to the broad ranges of stimulant effects in humans and to the widespread use of these agents in the treatment of hyperkinetic children. The acute and chronic behaviorally activating effects of opioids will be characterized in rats and the role of opioid receptor mediated mechanisms and monoamine systems underlying the various response components will be investigated using a variety of pharmacological, neurochemical, and discrete intracerebral injection techniques. Similar behavioral and mechanistic studies are also planned to compare and contrast the activating effects of putative sigma receptor agonists (e.g., SKF-10,047) and PCP with those produced by morphine-like agents (mu-receptor agonists) and opioid peptides. In addition, a series of experiments will be directed at further examining the role of endogenous opioid systems in the opiate-like response activation associated with mild stress. Our research concerning opioid-induced alterations of stimulus-directed behavior will also be continued. Opioid-induced behavioral activation may be relevant to narcotic euphoria and drug-seeking behavior and, in addition, may serve as an appropriate animal behavior model for various forms of psychopathology in which endogenous opioids have been inplicated.