PET BIOCHEMICAL MECHANISMS OF ALTERATIONS IN MOOD

宠物情绪变化的生化机制

• 批准号: 3376401
• 负责人: MICHAEL E PHELPS
• 金额: $ 59.03万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-06-01 至 1993-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3376401
• 关键词: Macaca; amphetamines; antidepressants; auditory stimulus; behavior test; brain imaging /visualization /scanning; brain metabolism; central nervous system stimulants; chemical synthesis; clinical biomedical equipment; cocaine; cognition; deoxyglucose; dopamine receptor; drug addiction; experimental brain lesion; glucose metabolism; human subject; laboratory rat; memory; methylphenidate; neuropsychology; obsessive compulsive disorder; oxygen consumption; positron emission tomography; psychobiology; psychopharmacology; radionuclide diagnosis; radiopharmacology; radiotracer; visual stimulus

The overall goal of this proposal is to develop and apply methods for the tracer kinetic radioassay of dopaminergic systems in the mammalian brain. This approach will combine animal experimentation and human studies with positron emission tomography (PET). The proposed studies will build upon our presently funded work to extend the availability of biochemical probes (e.g., substrate analogs, receptor binding ligands, and enzyme suicide inhibitors) to the study of dopaminergic function in health and disease. Tracer kinetic modeling approaches will be used to determine efficient ways of monitoring brain energy metabolism during behavioral tasks and of enhancing the specificity, delivery and localization of dopamine specific tracers in the central nervous system. A new human PET instrument, that we have developed, will be applied to these studies; it will provide unprecedented spatial resolution and sampling abilities. An animal PET device will be developed (funded from other sources: DOE) and applied in this proposal; it will provide spatial resolution approaching the theoretical limit for PET instruments. Anatomical methods for data analysis will optimize the localization of neurochemical sites in both human and animal brains. Validated biochemical probes of dopaminergic function will be tested during perturbations of dopamine networks in the brain (e.g., electrical stimulation, chemical stimulation, degenerative states (MPTP), lesions, behavioral tasks, and neuropsychiatric disorders). The distribution of dopaminergic sites and their quantitative function both pre- and post-synaptically will be evaluated in normal states, during motor tasks, under the influence of dopamine stimulant drugs, and in patients with spontaneous (depression and obsessive- compulsive disorder) and drug-induced (cocaine and amphetamine addiction) alterations in mood.

该提案的总体目标是开发和应用方法 用于多巴胺能系统的示踪剂动力学放射测定 哺乳动物的大脑。 这种方法将结合动物实验 以及正电子发射断层扫描（PET）的人类研究。 这 拟议的研究将以我们目前资助的工作为基础 扩展生化探针的可用性（例如底物 类似物，受体结合配体和酶自杀抑制剂） 研究健康和疾病中多巴胺能功能。 示踪动力学建模方法将用于确定 监测脑能量代谢的有效方法 行为任务以及增强特异性，交付和 多巴胺特异性示踪剂的定位 系统。 我们开发的一种新的人类宠物乐器将 适用于这些研究；它将提供前所未有的空间 分辨率和抽样能力。 动物宠物装置将是 开发（由其他来源资助：DOE）并应用于此 提议;它将提供接近的空间分辨率 宠物仪器的理论极限。 数据解剖方法 分析将优化神经化学位点的定位 人类和动物的大脑。 经过验证的生化探针 多巴胺能功能将在扰动期间进行测试 大脑中的多巴胺网络（例如，电刺激， 化学刺激，退化状态（MPTP），病变， 行为任务和神经精神疾病）。 这 多巴胺能位点的分布及其定量功能 突触前后都将在正常状态进行评估， 在运动任务期间，在多巴胺刺激的影响下 药物，以及自发的患者（抑郁和强迫症） 强迫症）和药物诱导（可卡因和苯丙胺 成瘾）情绪改变。