NEUROCHEMISTRY OF DRUG ABUSE

这是为J.B.贾斯蒂斯，Jr.颁发研究科学家奖的请求 埃默里大学化学教授。这样做的长期目标是 研究是对生物多样性的生物学意义的理解 中枢神经几种结构中的神经递质多巴胺 关于它在药物滥用中的作用的信息系统。四个调查领域 计划：1)活体测量的基本问题 神经递质；2)奖赏的神经化学；3)神经化学 慢性可卡因的影响；4)反应的个体差异 可卡因。 提出了一种实验，以测试体内的一种新的解释 微透析结果，并利用这些新发现来研究 药物滥用的神经化学。重要的是要有一个明确的 理解微透析实验中产生的数据以避免 在药物研究中，对微透析的误解越来越多 虐待。拟议的基础研究适用于所有发射机系统， 不仅仅是目前正在研究的多巴胺能系统。 在第二组实验中，不同DA的相对重要性 将使用自我管理来评估可卡因滥用的途径 范例。本研究的目的是重新评估相对的 几种DA终末区域和胞体区域的贡献 可卡因的强化作用。使用的特定方法，即本地方法 在静脉给药期间脑部注射可卡因， 将有助于澄清除核以外的结构的程度 伏隔对可卡因的增强作用有贡献。 在第三组实验中，神经化学扰动导致 将在DA系统中对长期给予可卡因进行活体评估 使用微渗析和伏安法。合成、新陈代谢的改变， 释放、摄取和细胞外基础水平将在体内确定。 作为慢性治疗后时间的函数。的个体差异 这些与可卡因反应有关的过程将在 第四组实验。 这些实验的结果将有助于指导未来的体内实验 监测与滥用药物有关的神经化学过程。一个 更好地了解药物诱导的神经化学和神经解剖学 加强将有助于开发药物治疗的方法 虐待。

This is a request for a Research Scientist Award for J. B. Justice, Jr., Professor of Chemistry, Emory University. The long term objective of this research is the understanding of the biological significance of the neurotransmitter dopamine (DA) in several structures in the central nervous system with respect to its role in drug abuse. Four areas of investigation are planned: 1) fundamental questions of in vivo measurement of neurotransmitters; 2) the neurochemistry of reward; 3) neurochemical effects of chronic cocaine; 4) individual differences in response to cocaine. Experiments are proposed which will test a new interpretation of in vivo microdialysis results and exploit these new findings to study the neurochemistry of drug abuse. It is essential to have a clear understanding of the data generated in microdialysis experiments to avoid misinterpretations as microdialysis is increasingly used in studies of drug abuse. The proposed fundamental studies apply to all transmitter systems, not just the dopaminergic system currently under investigation. In the second group of experiments, the relative importance of different DA pathways in cocaine abuse will be assessed using the self-administration paradigm. The aim of the present study is to reassess the relative contribution of several DA terminal fields and cell body regions in the reinforcing effects of cocaine. The particular methods used, that is local intracranial injection of cocaine during intravenous self-administration, will help to clarify the extent that structures other than the nucleus accumbens contribute to the reinforcing effects of cocaine. In the third group of experiments, the neurochemical perturbations caused by chronic cocaine administration will be assessed in vivo in DA systems using microdialysis and voltammetry. Alterations in synthesis, metabolism, release, uptake, and basal extracellular level will be determined in vivo as a function of time after chronic treatment. Individual differences in these processes with respect to response to cocaine will be assessed in the fourth group of experiments. The results of these experiments will help to guide future in vivo monitoring of neurochemical processes associated with abuse of drugs. A better understanding of the neurochemistry and neuroanatomy of drug induced reinforcement will help in developing approaches to treatment of drug abuse.