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IS CHRONIC COCAINE ABUSE TOXIC TO THE HUMAN BRAIN?

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:
依托单位国家:
美国
项目类别:
财政年份:
1991
资助国家:
美国
项目状态:
已结题
起止时间:
1991-08-01 至 1994-07-31

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中文摘要
翻译
尽管可卡因滥用呈爆炸性增长,但几乎没有信息显示 在人类大脑中,长期的 接触到这种药物。我们研究的主要目的是为了 第一次,对行为进行了系统和全面的检查 可卡因尸检脑中的主要神经递质系统 施虐者。我们建议测试慢性可卡因的特定假设 虐待将与尸检人类的长期耗尽有关 大脑中单胺类神经递质的标志物 高效液相色谱、定量放射自显影、受体结合和光亲和力 贴标签的程序。 身体解剖可卡因滥用的大脑(在接下来的三年中每年10例) 将从一名加拿大人的250多具可能的尸检中精心挑选 (多伦多)和两个美国(明尼阿波利斯;纽约州布朗克斯)中锋。所获得的 神经化学数据将与年中获得的生化结果进行比较 两组药物(慢性海洛因;酒精)和一组非神经系统疾病组。 所有申请者都在相关的人力资源方面表现出了专业知识。 脑部解剖、神经化学和神经病理成分 调查。 现在,许多努力都被用于设计实验动物研究 了解可卡因成瘾的生化基础及其长期作用 慢性可卡因滥用后大脑的变化。我们认为,这样的 更合适的研究应该在人脑中进行。我们 建议我们深入研究的结果将为第一次 时间,关于潜在的长期的基线信息 可卡因的药理/神经毒理作用以及 制定人类可卡因新治疗策略的跳板 施虐者。
英文摘要
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.
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