BRAIN NEUROCHEMISTRY OF HUMAN METHAMPHETAMINE USERS

描述：申请者摘要 尽管甲基苯丙胺(MA)在美国被严重滥用， 关于这种药物对大脑影响的信息在很大程度上仅限于 动物研究。动物研究的结果在多大程度上 对人类一概而论尚不清楚。 宽广的目标。我们的总体目标是确定大脑中的这些变化 人类长期服用MA可能是导致行为的原因 以及长期接触毒品可能产生的神经毒理后果。 明确的目标。在上一个资助期内，我们展示了 人体MA使用者尸检脑内神经化学变化提示 MA可能在多巴胺受体连接的途径中产生变化，并可能 导致氧化应激。我们的主要具体目标是确定 多巴胺受体调节的腺酰环化酶活性是否发生改变 脑组织氧化应激和损伤指数水平升高 人类MA用户。 设计。将在尸检的脑组织中测量神经化学指标 慢性MA吸毒者、匹配的对照组和可卡因吸毒者的大脑 和海洛因使用者作为疾病控制组。 健康相关性：我们预计我们的调查、利用和我们的 知识，唯一收集的人类大脑尸检样本来自 长期使用MA的用户，将提供独特且重要的相关信息 对人类长期接触MA的行为影响。它也是 重要的是要知道MA是否会导致人体氧化应激和损伤 大脑。最终，这些数据可能有助于开发新的 解决吸毒成瘾问题的方法。

DESCRIPTION: Applicant's Abstract Although methamphetamine (MA) is significantly abused in the U.S., information on the effects of the drug on the brain is largely limited to animal studies. The extent to which the results of animal studies generalize to the human is not known. Broad objective. Our broad objective is to identify those changes in brain of human chronic users of MA which may be responsible for the behavioural and possible neurotoxicological consequences of long-term drug exposure. Specific aims. During the previous funding period, we demonstrated neurochemical changes in autopsied brain of human MA users suggesting that MA may produce alterations in a dopamine receptor-linked pathway and might cause oxidative stress. Our major specific aims are to establish whether dopamine receptor-modulated adenylyl cyclase activity is altered and whether levels of indices of oxidative stress and damage are increased in brain of human MA users. Design. Neurochemical indices will be measured in autopsied brain of chronic MA users, a matched control group, and in brain of users of cocaine and users of heroin as disease control groups. Health relevance: We expect that our investigation, utilizing, to our knowledge, the only collection of autopsied human brain specimens from long-term MA users, will provide unique and important information relevant to the behavioural effects of chronic MA exposure in the human. It is also important to know whether MA causes oxidative stress and damage in human brain. Ultimately, these data may contribute to the development of new approaches to the problem of drug addiction.