PSYCHOPHARMACOLOGY OF STIMULANTS AND OPIOID PEPTIDES

这份申请书描述了一项为期五年的研究计划，以研究 兴奋剂和阿片类药物的精神药理学。这项研究将利用 许多不同的方法，包括行为学。药理上的， 神经化学和电生理技术进一步表征 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，我们已经确定了 一般行为特征或维度(例如，坚持性和 环境参与)，这区分了响应简档 与不同类型的兴奋剂相关，似乎超越了 物种差异。我们已经制定了操作定义的措施， 这些行为维度包含了各种特定的反应 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。这个 我们提出的刺激性反应的明显普遍特征 在大鼠身上的研究可能与广泛的刺激效应有关 以及这些药物在人类治疗中的广泛使用 多动症儿童。 阿片类药物的急性和慢性行为激活效应将是 大鼠的特点及阿片受体介导的作用机制 而作为各种反应成分基础的单胺系统将是 使用各种药理、神经化学和 分立脑内注射技术。相似的行为和 还计划进行机制研究，以比较和对比激活 可能的Sigma受体激动剂(如SKF-10,047)和PCP的作用 由吗啡类药物(Mu受体激动剂)和阿片类药物产生的 多肽。此外，还将进行一系列实验，以进一步 检查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。我们的研究涉及到 阿片类药物诱导的刺激导向行为的改变也将是 继续。阿片类药物诱导的行为激活可能与 麻醉性快感和寻求毒品行为，此外，还可以作为 一种适用于各种形式精神病理学的动物行为模型 其中涉及内源性阿片类药物。

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.