MDMA-INDUCED NEUROTOXICITY - PARAMETERS OF DEGENERATION AND RECOVERY OF BRAIN-SEROTONIN NEURONS
MDMA-INDUCED NEUROTOXICITY - PARAMETERS OF DEGENERATION AND RECOVERY OF BRAIN-SEROTONIN NEURONS
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DOI：
10.1016/0091-3057(88)90155-4
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发表时间：
1988-02-01
影响因子：
3.6
通讯作者：
DESOUZA, EB
中科院分区：
文献类型：
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作者：
BATTAGLIA, G;YEH, SY;DESOUZA, EB
本研究探讨了影响3，4-亚甲二氧基甲基苯丙胺（MDMA）对脑内5-羟色胺（5-HT）神经元毒性作用的一些参数。注射MDMA的剂量和次数均影响对5-HT轴突和末梢的神经毒性程度，如通过5-HT和5-羟基吲哚乙酸（5-HIAA）含量和5-HT摄取位点密度的降低所评估的。重复全身给予不同剂量的MDMA（5-20 mg/kg，每天两次，连续4天）导致5-HT、5-HIAA和5-HT吸收部位呈剂量依赖性减少。增加注射MDMA的次数导致5-HT和5-HIAA的减少逐渐增加，这发生在5-HT摄取部位减少之前。相比之下，单次或重复注射20 mg/kg MDMA后，未观察到去甲肾上腺素摄取部位的密度发生显著变化。在神经元再生方面，在用MDMA治疗后，5-HT摄取位点的初始90%损失之后，这些位点的恢复发生在一段延长的时间内;在6个月时观察到显著减少25%，并且在用MDMA治疗后12个月时5-HT摄取位点的浓度恢复到对照水平。在每次注射MDMA之前，使用选择性5-HT摄取阻断剂西酞普兰进行预处理，可防止MDMA对上述5-HT参数的神经毒性作用，表明大脑5-HT参数的主动摄取MDMA或MDMA相关物质，表明大脑5-HT神经元的主动摄取MDMA或MDMA相关物质参与了药物的神经毒性作用。此外，MDMA对5-HT神经元的神经退行性作用表现出一定的种属特异性，因为在大鼠和豚鼠中观察到大脑皮质5-HT、5-HIAA和5-HT摄取部位的类似降低，而在小鼠脑中未观察到任何这些多巴胺能参数的显著变化。
This study investigates a number of parameters that influence the neurotoxic effects of 3,4-methylenedioxymethamphetamine (MDMA) on serotonin (5-HT) neurons in brain. Both the dose and number of injections of MDMA affect the degree of neurotoxicity on 5-HT axons and terminals as assessed by decreases in the content of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) and the density of 5-HT uptake sites. Repeated systemic administration of various doses of MDMA (5-20 mg/kg twice daily for 4 consecutive days) results in dose-dependent decreases in 5-HT, 5-HIAA and 5-HT uptake sites. Increasing the number of injections of MDMA resulted in progressively greater reductions in 5-HT and 5-HIAA which occurred prior to decreases in 5-HT uptake sites. In contrast, no significant changes were observed in the density of norepinephrine uptake sites following single or repeated injections of 20 mg/kg MDMA. With respect to neuronal regeneration, following an initial 90% loss of 5-HT uptake sites after treatment with MDMA, the recovery of these sites occurred over a protracted period of time; a marked 25% reduction was seen at 6 months and the concentration of 5-HT uptake sites returned to control levels at 12 months following treatment with MDMA. Pretreatment with the selective 5-HT uptake blocker, citalopram, prior to each injection of MDMA prevented the neurotoxic effects of MDMA on the 5-HT parameters described above suggesting that active uptake MDMA or a MDMA-related substances into brain 5-HT parameters described above suggesting that active uptake of MDMA or a MDMA-related substance into brain 5-HT neurons was involved in the neurotoxic actions of the drug. In addition, the neurodegenerative effects of MDMA on 5-HT neurons exhibited some species specificity as comparable decreases in cerebral cortical 5-HT, 5-HIAA and 5-HT uptake sites were observed in rat and guinea pig while no significant changes in any of these serotonergic parameters were seen in mouse brain.