AMPHETAMINE INDUCED MONOAMINERGIC NEUROTOXICITY IN ANIMALS & HUMANS

目前的项目包括对啮齿动物、非人类灵长类动物的研究。 和人类。各种苯丙胺类似物的神经毒性潜力， 包括(+/-)3，4-亚甲基二氧甲基苯丙胺、甲基苯丙胺、 芬氟拉明和美卡西酮是首先在动物身上确定的，而 多种生物检测方法在神经毒性检测中的应用 是有决心的。使用的方法包括直接的神经化学测量 单胺，它们的代谢产物，它们的合成酶和它们的 传送者。如果需要，使用免疫荧光的解剖学研究 还进行了正电子发射断层扫描(PET)等技术。 使用放射性药物选择性标记单胺能的研究 传送者。对人体的研究旨在确定 在动物中发现的神经毒性也在接触这些物质的人类中发现。 药物，如果是这样的话，这种损害的功能后果。方法 使用的包括脑脊液(CSF)措施 5-羟基吲哚乙酸(5-HIAA)，PET研究，疼痛测试，睡眠 研究、神经内分泌挑战、认知测试和各种 精神测试。到目前为止，上述所有化合物都已被证明 对啮齿动物的5-羟色胺神经元和/或多巴胺神经元有神经毒性 以及非人类灵长类动物。脑脊液研究和正电子发射计算机断层扫描研究都显示 是检测单胺类神经毒性的有效方法。在……里面 人类，已经确定MDMA使用者有选择性的减少 在脑脊液5-HIAA中，对m-CPP的神经内分泌和行为反应迟钝， 5-羟色胺激动剂，减少5-羟色胺转运体 宠物，睡眠结构的改变。以及认知能力的下降 需要持续关注和算术计算的任务。 甲基苯丙胺和美卡西酮使用者被发现患有 PET显示，多巴胺转运蛋白显著减少。 正在进行的研究旨在扩大这些发现。

The present project is comprised of studies in rodents, non-human primates and humans. The neurotoxic potential of a variety of amphetamine analogs, including (+/-) 3,4-methylenedioxymethamphetamine, methamphetamine, fenfluramine and methcathinone, is first determined in animals, and the utility of various biological assays for the detection of neurotoxicity are determined. Methods used include direct neurochemical measures of monoamines, their metabolites, their synthetic enzymes, and their transporters. When indicated, anatomical studies using immunofluorescent techniques are also conducted, as are positron emission tomography (PET) studies using radiopharmaceuticals that selectively label monoaminergic transporters. Studies in humans are designed to determine whether neurotoxicity seen in animals is also seen in humans exposed to these drugs, and if so, the functional consequences of this damage. Methods utilized include cerebrospinal fluid (CSF) measures of 5-hydroxyindoleacetic acid (5-HIAA), PET studies, pain testing, sleep studies, neuroendocrine challenges, cognitive testing, and a variety of psychiatric tests. To date, all of the above compounds have been shown to be neurotoxic to serotonin neurons, dopamine neurons, or both, in rodents and non-humans primates. CSF studies and PET studies have both been shown to be valid methods for detecting monoaminergic neurotoxicity. In humans, it has been determined that MDMA users have selective decreases in CSF 5-HIAA, blunted neuroendocrine and behavioral responses to m-CPP, a serotonin agonist, decreased serotonin transporters as visualized by PET, alterations in sleep architecture. and decrements in a cognitive task requiring sustained attention and arithmetic calculation. Methamphetamine and methcathinone users have been found to have significant decreases in the dopamine transporter, as visualized by PET. Ongoing studies are aimed at extending these findings.