PSYCHOPHARMACOLOGY OF STIMULANTS AND OPIOID PEPTIDES

兴奋剂和阿片肽的精神药理学

• 批准号: 3076163
• 负责人: DAVID S SEGAL
• 金额: $ 8.15万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-12-01 至 1994-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3076163
• 关键词: acetylcholine; amphetamines; caffeine; central nervous system stimulants; cocaine; corpus striatum; dialysis therapy; dopamine; dosage; ethology; laboratory rat; limbic system; microdialysis; neurochemistry; neuroendocrine system; neurotransmitter receptor; noise; opiate alkaloid; psychological stressor; psychoneuroimmunology; psychopharmacology; serotonin; stress

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.

这份申请书是由 研究科学家奖概述了一项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 旨在表征急性（第1节）和慢性（第 II）兴奋剂对各种行为成分的影响， 我们已经确定的维度。 将特别强调 旨在研究过渡剂量， 反应模式的个体差异可能更多 很容易被归类为亚组。 行为评价 差分响应曲线的基础已被证明是重要的 在确定各种行为之间的关系， 成分和神经化学系统和机制， AMPH效应。 这些结果的一般性将进一步 通过详细评估其他苯丙胺类 兴奋剂，包括可卡因、哌醋甲酯和阿扑吗啡， 通过与其他精神兴奋剂的比较， 比如咖啡因。 除了系统地评价 单胺系统在各种组分中的作用 刺激反应，具体的实验将解决 假设的机制subserving行为维度 （第三节）。 实验还旨在评估所谓的 压力在刺激反应中的作用。 初步研究将 进一步表征噪声刺激的影响， 安非他明对各种行为，神经化学，神经内分泌 和免疫措施，以便为 评估潜在的应激刺激机制 交互. 第四部分介绍了我们的研究， 在自由活动的动物中进行微透析程序， 完善我们对刺激诱导的 纹状体DA、5 HT和Ach动力学的变化。 体外技术 将用于进一步研究D1和D2 DA的关系 受体激活的外观的特定成分的 刻板的反应。 这些体内和体外方法将 扩展到中脑边缘DA系统，以确定 中脑纹状体和中脑边缘多巴胺激活的关系 对AMPH的行为特征有影响 最后我们将 检查重复AMPH预处理的效果，以确定 急性反应中的神经化学变化 有助于行为增强， AMPH给药。 这些研究的结果应能提高 我们对特定行为神经化学关系的理解 船舶受到兴奋剂的急性和慢性影响。