CENTER FOR STUDY OF NEUROREGULATORS AND DRUGS OF ABUSE

这个NIDA中心补助金申请是为了研究 药物滥用的生物医学方面，主要侧重于配体- 感受器过程 核心目标是使用 分子生物学和肽化学来研究 阿片系统，包括其配体、受体和 以协调的方式加工酶，以研究 药物的不同、区域特异性和与时间相关的作用 虐待 这项研究最终将允许开发 用于鉴别诊断临床研究的人体探针， 治疗和预防。 这项研究是针对药物的潜在机制 耐受性，最终成瘾和戒断， 强调天然存在的内啡肽或阿片肽 在药物滥用中起关键作用的神经组织中。 的 具体目标是研究：1）阿片样物质前体， 处理和调节，以确定 天然存在的物质是如何被控制的， 受滥用药物影响; 2）处理阿片类药物的酶 通过克隆它们并研究它们的正常调节， 以及它们是如何被滥用药物改变的;以及3）受体 通过克隆阿片类药物并研究其调节， 因为受体可能是理解 毒品 作为该中心的一部分，其他药物滥用系统也将 接受检查。 拟议的计划扩大了正在进行的研究的成员， 中心利用蛋白质和肽化学技术 （包括肽合成、免疫测定、肽和蛋白质） 分子生物学（包括cDNA克隆和mRNA 组织化学（包括光和电镜） 免疫细胞化学和原位杂交）;分析 神经化学（包括快原子轰击质量 光谱）;和人类研究的跨学科和 综合方式。 更准确地理解 产生的耐受、成瘾和戒断机制， 这些研究和探索，为提高 诊断、治疗和预防药物滥用的方法。

This NIDA Center Grant application is for studies of the biomedical aspects of drug abuse with a primary focus on ligand- receptor processes. The central goal is to use the tools of molecular biology and peptide chemistry to study key processes of the opioid systems including their ligands, receptors, and processing enzymes in a coordinated manner to investigate the differential, region-specific and time-related effects of drugs of abuse. The research ultimately will permit the development of human probes for clinical investigation of differential diagnosis, treatment, and prevention. The research is oriented to the mechanisms underlying drug tolerance and ultimately addiction and withdrawal with special emphasis on the endorphins, or opioid peptides, naturally present in nervous tissue which have a key role in drug abuse. The specific goals are to study: 1) opioid precursors in terms of their processing and regulation in order to determine the ways in which the naturally present substances are controlled and how they are affected by drugs of abuse; 2) enzymes which process opioid peptides by cloning them and investigating their normal regulation and how they are altered by drugs of abuse; and 3) the receptors of the opioids by cloning them and investigating their regulation since the receptors may be key to understanding the effects of drugs. As parts of the Center, other drug abuse systems will also be examined. The proposed program expands ongoing studies of members of the Center using the techniques of protein and peptide chemistry (including peptide synthesis, immunoassays, peptide and protein isolation); molecular biology (including cDNA cloning and mRNA techniques); histochemistry (including light and EM immunocytochemistry and in situ hybridization); analytical neurochemistry (including fast atom bombardment mass spectrometry); and human studies in a cross-disciplinary and integrated manner. The more precise understanding of the mechanisms of tolerance, addiction, and withdrawal yielded by the studies and the probes should provide the basis for improving methods of diagnosis, treatment, and prevention of drug abuse.