NEUROCHEMISTRY OF DRUG ABUSE

这是为J. B申请研究科学家奖的申请。小贾斯蒂丝 埃默里大学化学教授。 这一长期目标 研究是对生物学意义的理解， 在中枢神经系统的几个结构中的神经递质多巴胺（DA） 在药物滥用方面的作用。 四个调查领域 计划：1）体内测量的基本问题， 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）个体差异， 可卡因 提出了实验，这将测试一个新的解释，在体内 微透析结果，并利用这些新的发现来研究 药物滥用的神经化学 必须有一个明确的 了解微透析实验中产生的数据，以避免 随着微透析越来越多地用于药物研究， 虐待 所提出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 可卡因滥用的途径将使用自我管理评估 范例 本研究的目的是重新评估相对 几个DA终端领域和细胞体区域的贡献， 可卡因的强化作用 所使用的特定方法，即本地 在静脉内自我给药期间颅内注射可卡因， 将有助于阐明细胞核以外的结构 可卡因会增强可卡因的药效。 在第三组实验中， 将在DA系统中进行体内评估 使用微透析和伏安法。 合成代谢的改变， 将在体内测定释放、摄取和基础细胞外水平 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。 这些实验结果将有助于指导今后的体内 监测与药物滥用有关的神经化学过程。 一 更好地理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.