IS CHRONIC COCAINE ABUSE TOXIC TO THE HUMAN BRAIN?

长期滥用可卡因对人脑有毒吗？

• 批准号: 3213833
• 负责人: STEPHEN John KISH
• 金额: $ 6.12万
• 依托单位: UNIVERSITY OF TORONTO
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-01 至 1994-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3213833
• 关键词: Rodentias; affinity labeling; autoradiography; biomarker; brain metabolism; cerebral cortex; cocaine; corpus striatum; dopamine; drug addiction; high performance liquid chromatography; histopathology; human tissue; neurochemistry; neurotoxins; neurotransmitter metabolism; nucleus accumbens; postmortem; receptor binding; self stimulation; tissue /cell preparation

Despite the explosive increase in cocaine abuse, little information is available with respect to the effects, in human brain, of long-term exposure to this drug. The major objective of our study is to conduct, for the first time, a systematic and comprehensive examination of the behaviour of the major neurotransmitter systems in autopsied brain of cocaine abusers. We propose to test the Specific Hypothesis that chronic cocaine abuse will be associated with long-lasting depletion in autopsied human brain in the markers for the monoamine neurotransmitters as assessed by HPLC, quantitative autoradiography, receptor binding, and photoaffinity labelling procedures. Autopsied cocaine-abused brain (n=10 per year for the next three years) will be carefully selected from over 250 possible autopsies at one Canadian (Toronto) and two U.S. (Minneapolis; Bronx, N.Y.) centers. The obtained neurochemical data will be compared with biochemical findings obtained in two drug (chronic heroin; alcohol) and one non-neurological group. All of the applicants have demonstrated expertise in the relevant human brain dissection, neurochemical, and neuropathological components of this investigation. Much effort is now being directed to experimental animal studies designed to understand the biochemical basis of cocaine addiction and the long-term changes in brain following chronic cocaine abuse. We argue that such studies should more appropriately be conducted in the human brain. We suggest that the results of our intensive study will provide, for the first time, baseline information with respect to the potential long-term pharmacologic/neurotoxicological efforts of cocaine as well as a springboard for formulating new treatment strategies for the human cocaine abuser.

尽管可卡因滥用呈爆炸性增长， 在人类大脑中， 暴露于这种药物。 我们研究的主要目的是， 第一次，对行为进行系统和全面的检查， 可卡因尸检大脑中的主要神经递质系统 施虐者 我们建议测试特定假设，慢性可卡因 虐待将与长期消耗尸检的人 脑中的单胺神经递质的标记物，如通过 HPLC、定量放射自显影、受体结合和光亲和性 标签程序。 尸检可卡因滥用的大脑（n=10，未来三年每年） 将从250多个可能的尸检中精心挑选， （多伦多）和两个美国（明尼阿波利斯;纽约布朗克斯）中心. 所获得的 神经化学数据将与在以下研究中获得的生化结果进行比较： 两个药物组（慢性海洛因;酒精）和一个非神经组。 所有申请人都表现出相关人类的专业知识 大脑解剖，神经化学和神经病理学成分，这是 调查 现在正致力于动物实验研究， 了解可卡因成瘾的生化基础和长期的 慢性可卡因滥用后大脑的变化 我们认为，这种 更适合在人脑中进行研究。 我们 我认为，我们深入研究的结果将首先提供 时间、关于潜在长期 可卡因的药理学/神经毒理学研究以及 制定人体可卡因新治疗策略的跳板 施虐者