CENTER FOR STUDY OF NEUROREGULATORS AND DRUGS OF ABUSE

这份NIDA中心拨款申请是为了研究 药物滥用的生物医学方面，主要集中在配体- 受体过程。中心目标是使用以下工具 分子生物学和多肽化学研究关键过程 阿片系统包括它们的配体、受体和 以协调的方式处理酶以调查 药物的差异性、地区特异性和时间相关效应 虐待。这项研究最终将允许开发 用于临床鉴别诊断研究的人体探针， 治疗和预防。 这项研究针对的是药物的潜在机制。 宽容，并最终上瘾和戒除与特殊 强调内啡肽，或阿片肽，自然存在 在神经组织中，它在药物滥用中起关键作用。这个 具体目标是研究：1)阿片前体 处理和调节，以确定以下方式 自然存在的物质受到控制，以及它们是如何 受滥用药物的影响；2)处理阿片类药物的酶 克隆多肽并研究它们的正常调节 以及滥用药物如何改变它们；以及3)受体 通过克隆阿片类药物并研究它们的调节 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。 拟议的计划扩大了对联合国儿童基金会成员的持续研究 使用蛋白质和多肽化学技术的中心 (包括多肽合成、免疫分析、多肽和蛋白质 分离)；分子生物学(包括基因克隆和信使核糖核酸 技术)；组织化学(包括光和EM 免疫细胞化学和原位杂交)；分析性 神经化学(包括快原子轰击质量 光谱学)；以及跨学科和 整合的方式。越能准确地理解 产生耐受、成瘾和戒断的机制 这些研究和探索应该为改进提供基础 药物滥用的诊断、治疗和预防方法。

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.