MDMA NEUROTOXICITY IN PRIMATE: PERMANENT OR TRANSIENT?

MDMA是一种流行的娱乐性药物， 啮齿类动物和非人类灵长类动物大脑中的神经末梢。 目前还不清楚这种损害是可逆的还是永久的， 但鉴于最近的初步发现，这是一个重要的问题 这表明使用MDMA的人可能会引起中枢神经系统的兴奋， 神经元损伤 这项研究的目的是描述 MDMA对大鼠B#核内多巴胺能神经元的长期作用 非人类灵长类动物，并定义决定是否 MDMA的毒性作用是可逆的或永久性的。 第一组研究将检查神经元 MDMA治疗的猴中的恢复， 能神经纤维受损，但中缝无胞体丢失 原子核。 初步研究表明血清素的部分恢复 发生在这些动物身上超过十周的时间。 这一发现 将通过（1）测量其他化学品 5-羟色胺能纤维的标记物（5-羟色胺吸收位点和5-羟色胺吸收位点） 羟基吲哚乙酸浓度），（2）建立 各脑区恢复的时间进程和程度，（3） 确定神经化学恢复是否与 再生的神经纤维和（4）调查，如果 再生纤维的分布和外观， 正常 这些研究的结果应该能提供信息， 关于MDMA对中枢神经系统的长期影响 非人类灵长类动物的神经元，并可能证明直接相关 对患有MDMA诱导的神经元损伤的人。 第二组研究将试图确定 MDMA对中枢神经系统产生永久性毒性作用， 灵长类动物的神经元 特别是，将审查是否 更高或更受保护的MDMA剂量方案导致 中缝核中的肾上腺素能神经细胞体的破坏。 在这种情况下，不可逆转的影响当然会 预期。 确定MDMA的给药方案， 产生广泛的破坏神经元能神经细胞体 可以有很多有用的应用。 MDMA给药猴， 大脑血清素的大量永久性消耗 为了确定肾上腺素能神经元在大脑中的功能作用， 灵长类大脑 对这些动物的研究也可以提供有价值的 对表现出生化异常的人的临床评估指南 MDMA诱导的多巴胺能神经元损伤的证据。 这一发现 更高或更长剂量的MDMA会产生不可逆的 对肾上腺素能神经元的影响也具有重要意义。 对于那些反复使用高剂量这种药物的人来说 药 这项研究的长期目标是进一步确定 灵长类动物脑中多巴胺能神经元的功能作用， 描述MDMA中毒的长期后果， 人类和非人类灵长类动物。

MDMA is a popular recreational drug that damages serotonergic nerve terminals in the brain of rodent as well as non-human primates. Whether the damage is reversible or permanent is currently unknown, but this is an important question given recent preliminary findings indicating that humans who use MDMA may incur central serotonergic neuronal damage. The purpose of this research is to characterize the long-term effects of MDMA on serotonergic neurons in the b#in of non-human primates, and to define factors that determine whether the toxic effects of MDMA are reversible or permanent. The first set of studies will examine the potential for neuronal recovery in MDMA-treated monkeys that have sustained severe serotonergic nerve fiber damage, but no cell body loss in the raphe nuclei. Pilot studies indicate that partial recovery of serotonin takes place in these animals over a ten week period. This finding will be confirmed and extended by (1) measuring other chemical markers for serotonergic fibers (serotonin uptake sites and 5- hydroxyindoleacetic acid concentrations), (2) establishing the time-course and extent of recovery in various brain regions, (3) determining whether neurochemical recovery is related to regeneration of serotonergic nerve fibers and (4) investigating if the distribution and appearance of the regenerated fibers is normal. Results from these studies should yield information regarding the long-term effects of MDMA on central serotonergic neurons in non-human primates, and could prove directly relevant to humans who have sustained MDMA-induced neuronal damage. A second set of studies will attempt to identify conditions under which MDMA produces permanent toxic effects on central serotonergic neurons in the primate. In particular, it will be examined if higher or more protected dosage regimens of MDMA lead to destruction of serotonergic nerve cell bodies in the raphe nuclei. Under such conditions, irreversible effects would, of course, be anticipated. Identification of a dosage regimen of MDMA that produces extensive destruction of serotonergic nerve cell bodies could have several useful applications. MDMA-treated monkeys with a large and permanent depletion of brain serotonin could be used to define the functional role of serotonergic neurons in the primate brain. Studies in such animals could also provide valuable guidance for the clinical assessment of humans who show biochemical evidence of MDMA-induced serotonergic neuronal damage. The finding that higher or more protracted doses of MDMA produce irreversible effects on serotonergic neurons would also have important implications for those humans who use repeated high doses of this drug. The long-term objectives of this research are to further define the functional role of serotonergic neurons in the primate brain and to characterize the long-term consequences of MDMA intoxication in human and non-human primates.