Scanzello C R, Hatzidimitriou G, Martello A L, Katz J L, Ricaurte G A
Department of Neurology, Francis Scott Key Medical Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
J Pharmacol Exp Ther. 1993 Mar;264(3):1484-91.
(+/-)-3,4-Methylenedioxymethamphetamine (MDMA) is a recreational drug of abuse which damages serotonin (5-HT) neurons in animals. In monkeys, the damage appears to be permanent. By contrast, in rats there is indication that neuronal recovery takes place, although there is question as to whether the recovery is sustained. The purpose of the present study was to examine the fate of 5-HT neurons in MDMA-treated rats, and to compare findings in the rat with those in the monkey. Rats were treated with MDMA (10 mg/kg i.p.) every 2 hr for a total dose of 40 mg/kg. Two, 8, 16, 32 and 52 weeks later, groups (n = 8) of MDMA-treated rats, along with age-matched controls (n = 8), were analyzed for regional brain 5-HT, 5-hydroxyindoleacetic acid and [3H]paroxetine-labeled 5-HT uptake sites. Two weeks after MDMA, 5-HT neuronal markers were reduced markedly. Reductions ranged from 42 to 82% depending on brain region. By 16 weeks, there was evidence of recovery in some brain regions (e.g., hypothalamus and striatum) and by 32 weeks, recovery was nearly complete in most brain regions examined. One year after MDMA, recovery was still evidence in all brain regions evaluated, although closer inspection of the group data revealed that whereas most MDMA-treated rats recovered, some did not. These few animals had severe and enduring serotonergic deficits in multiple brain regions. Morphologic immunocytochemical studies yielded results which corroborated the neurochemical findings.(ABSTRACT TRUNCATED AT 250 WORDS)
（±）-3,4-亚甲基二氧甲基苯丙胺（摇头丸）是一种滥用的消遣性药物，会损害动物体内的5-羟色胺（5-HT）神经元。在猴子身上，这种损伤似乎是永久性的。相比之下，在大鼠身上有迹象表明神经元会恢复，尽管对于这种恢复是否能持续存在疑问。本研究的目的是检查用摇头丸处理过的大鼠中5-HT神经元的命运，并将大鼠的研究结果与猴子的进行比较。大鼠每2小时腹腔注射一次摇头丸（10毫克/千克），总剂量为40毫克/千克。在2周、8周、16周、32周和52周后，对用摇头丸处理过的大鼠组（n = 8）以及年龄匹配的对照组（n = 8）进行分析，检测大脑区域的5-HT、5-羟吲哚乙酸和[3H]帕罗西汀标记的5-HT摄取位点。摇头丸处理后2周，5-HT神经元标记物明显减少。减少幅度在42%至82%之间，具体取决于脑区。到16周时，一些脑区（如下丘脑和纹状体）有恢复的迹象，到32周时，在大多数检测的脑区恢复几乎完成。摇头丸处理一年后，在所有评估的脑区仍有恢复的迹象，尽管仔细检查组数据发现，虽然大多数用摇头丸处理过的大鼠恢复了，但有些没有。这几只动物在多个脑区有严重且持久的5-羟色胺能缺陷。形态学免疫细胞化学研究结果证实了神经化学研究结果。（摘要截断于250字）
