PSYCHOPHARMACOLOGY OF STIMULANTS AND OPIOID PEPTIDES

本申请由本公司提供续期薪酬支持 研究科学家奖概述了一个为期五年的研究计划 研究兴奋剂的神经精神药理学。研究是 旨在描述急性(第1节)和慢性(第1节) 二)兴奋剂对各种行为成分的影响以及 我们已经确定了维度。特别强调的是 针对以下情况的过渡剂量的调查 反应模式的个体差异可能更大 容易归类为子组的。对乘客的行为进行评估 事实证明，差异响应曲线的基础是重要的 在确定各种行为之间的关系时 成分和神经化学系统和机制 安非他明效应。这些结果的一般性将进一步 通过对其他苯丙胺类物质的详细评估进行检查 兴奋剂包括可卡因、哌甲酯和阿朴吗啡以及 通过将这些药物与其他精神运动兴奋剂进行比较 比如咖啡因。除了系统地评估 单胺系统在不同成分中的作用 刺激反应，具体的实验将解决 从属于行为维度的假设机制 (第III节)。实验也被设计用来评估所谓的 应激在刺激反应中的作用。初步研究将 进一步描述噪声刺激的影响和 苯丙胺对多种行为、神经化学、神经内分泌的影响 和免疫学措施，以提供基础 评估应激源-刺激剂潜在的可能机制 互动。 第四部分描述了我们使用活体进行的研究 在自由活动动物中的微透析程序延长和 完善我们对兴奋剂诱导的初步特征 纹状体多巴胺、5-羟色胺和乙酰胆碱的动态变化。体外技术 将被用来进一步检查d1和d2 DA的关系 受体激活到出现的特定成分 千篇一律的回答。这些体内和体外的方法将 被扩展到中间边缘DA系统，以确定如何 纹状体中脑区和边缘中脑区DA激活的关系 对安眠药的行为特征有贡献。最后，我们会 检测AMPH重复前处理的效果，以确定 神经化学变化是否与急性反应有关 有助于由重复导致的行为增强 AMPH管理。这些研究的结果应该加强 我们对特定行为-神经化学关系的理解-- 涉及兴奋剂的急性和慢性影响的船只。

This application for renewal of renewal of salary support by the research Scientist Award outlines a five-year program of research to study the neuropsychopharmacology of stimulants. Studies are designed to characterize the acute (Section 1) and chronic (Section II) effects of stimulants on the various behavioral components and dimensions we have identified. Particular emphasis will be directed at the investigation of transitional doses where individual differences in patterns of responsiveness may be more readily categorized into subgroups. Evaluation of behavior on the basis of differential response profiles has proven to be important in determining the relationship between the various behavioral components and the neurochemical systems and mechanisms underlying the AMPH effects. The generality of these results will be further examined by detailed assessment of other amphetamine-like stimulants including cocaine, methylphenidate and apomorphine and by comparison of these agents with other psychomotor stimulants such as caffeine. In addition to a systematic evaluation of the role of monoamine systems in the various components of the stimulant response, specific experiments will address the hypothesized mechanisms subserving the behavioral dimensions (Section III). Experiments are also designed to assess the alleged role of stress in the stimulant response. Initial studies will further characterize the effects of noise stimulation and amphetamine on various behavioral, neurochemical, neuroendocrine and immunological measures in order to provide a basis for evaluating possible mechanisms underlying stressor-stimulant interactions. The fourth section describes our research using in vivo microdialysis procedures in freely moving animals to extend and refine our preliminary characterization of stimulant induced changes in striatal DA, 5HT, and Ach dynamics. In vitro techniques will be used to examine further the relationship of D1 and D2 DA receptor activation to the appearance of specific components of the stereotyped response. These in vivo and in vitro approaches will be extended to the mesolimbic DA system to determine how the relationship between mesostriatal and mesolimbic DA activation contributes to the AMPH behavioral profile. Finally, we will examine the effects of repeated AMPH pretreatment to determine whether neurochemical changes implicated in the acute response contribute to the behavioral augmentation resulting from repeated AMPH administration. The results of these studies should enhance our understanding of specific behavioral-neurochemical relation- ships involved in the acute and chronic effects of stimulants.