MDMA NEUROTOXICITY IN PRIMATE: PERMANENT OR TRANSIENT?

MDMA是一种受欢迎的娱乐药物，可以损害5-羟色胺能神经 啮齿动物和非人灵长类动物大脑中的终末。 目前尚不清楚损害是可逆的还是永久性的， 但考虑到最近的初步发现，这是一个重要的问题。 这表明使用MDMA的人可能会引起中枢5-羟色胺能 神经元损伤。这项研究的目的是描述 亚甲基四氢叶酸对大鼠脑内5-羟色胺能神经元的长期影响 非人类灵长类动物，并定义决定是否 MDMA的毒性效应是可逆的或永久性的。 第一组研究将检验神经元的潜力。 接受MDMA治疗的猴子在经历了严重的 5-羟色胺能神经纤维损伤，但中缝未见胞体丢失 原子核。初步研究表明，5-羟色胺部分恢复 在这些动物身上发生的时间超过十周。这一发现 将通过(1)测量其他化学物质来确认和扩展 5-羟色胺能纤维的标志物(5-羟色胺摄取部位和5- 羟基吲哚乙酸浓度)，(2)建立 不同脑区恢复的时程和程度，(3) 确定神经化学恢复是否与 5-羟色胺能神经纤维的再生及(4)研究 再生纤维的分布和形貌为 很正常。这些研究的结果应该会提供信息 关于MDMA对中枢5-羟色胺能神经元的长期影响 非人灵长类动物中的神经元，并可能被证明与 对那些遭受MDMA诱导的神经元损伤的人类来说。 第二组研究将试图确定以下情况 哪种MDMA对中枢5-羟色胺能产生永久性毒性作用 灵长类动物的神经元。特别是，它将被审查是否 更高或更多保护性剂量的MDMA方案会导致 中缝核内5-羟色胺能神经元胞体破坏。 在这种情况下，不可逆转的影响当然是 已经预料到了。一种MDMA给药方案的鉴定 引起5-羟色胺能神经细胞体的广泛破坏 可能会有几个有用的应用。用MDMA治疗的猴子 脑部5-羟色胺的大量和永久性耗竭是可以使用的。 为明确5-羟色胺能神经元在脑内的功能作用 灵长类动物的大脑。对这类动物的研究也可能提供有价值的 对表现出生化反应的人类的临床评估指南 MDMA诱导的5-羟色胺能神经元损伤的证据。这一发现 更高剂量或更长时间的MDMA会产生不可逆转的 对5-羟色胺能神经元的影响也将是重要的 对那些反复使用高剂量这种药物的人的影响 毒品。 这项研究的长期目标是进一步界定 5-羟色胺能神经元在灵长类动物脑内的功能作用 为了描述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.