A study of the neurotoxic effect of MDMA ('ecstasy') on 5-HT neurones in the brains of mothers and neonates following administration of the drug during pregnancy
A study of the neurotoxic effect of MDMA ('ecstasy') on 5-HT neurones in the brains of mothers and neonates following administration of the drug during pregnancy
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DOI：
10.1038/sj.bjp.0701201
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发表时间：
1997-06-01
影响因子：
7.3
通讯作者：
Green, AR
中科院分区：
文献类型：
--
作者：
Colado, MI;OShea, E;Green, AR
[1]众所周知，3，4-亚甲二氧基甲基苯丙胺（MDMA或“迷魂药”）具有神经毒性，可使许多物种的大脑5-羟色胺（5-HT）神经末梢发生长期变性。由于亚甲二氧基甲基安非他明被年轻人广泛用作娱乐性药物，许多育龄妇女正在服用。因此，我们研究了在怀孕期间给予大鼠高剂量MDMA对母鼠和母鼠脑内容物的影响。在妊娠期的第14-17天每天注射两次。初始剂量在母鼠中产生显著的高热反应，在进一步给药后，其峰高和曲线下面积均逐渐减弱。在给药期间，母鼠体重下降。3 MDMA给药母鼠的窝仔数略有下降（-20%）。4分娩后1周，母鼠海马和纹状体中5-HT及其代谢产物5-HIAA的浓度下降超过65%，皮质中下降40%。相比之下，MDMA给药母鼠幼崽端脑背侧的5-HT和5-HIAA含量与对照动物所生幼崽组织中的含量相同。3 h和6 h后，大鼠皮质组织中硫代巴比妥酸反应物质（TEARS）增加，表明脂质过氧化作用增强。在3小时或6小时前注射该剂量MDMA的7-10天新生儿的皮质组织中未观察到泪液增加。6数据表明，与在母体大脑中观察到的损伤相反，在成熟阶段子宫内暴露于MDMA不会对胎鼠脑中的5-HT神经末梢造成损伤。这可能是由于MDMA在成人大脑中代谢为产生自由基的实体，但在未成熟大脑中不代谢，或者是由于未成熟大脑中存在更有效或更活跃的自由基清除机制。
1 It is well established that 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') is neurotoxic and produces long term degeneration of cerebral 5-hydroxytryptamine (5-HT) nerve terminals in many species. Since MDMA is used extensively as a recreational drug by young people, it is being ingested by many women of child bearing age. We have therefore examined the effect of administering high doses of MDMA to rats during pregnancy on the cerebral content of both the dams and the neonates.2 MDMA (20 mg kg(-1), s.c.) was injected twice daily on days 14-17 of the gestation period. The initial dose produced a marked hyperthermic response in the dam which was progressively attenuated in both peak height and area under the curve following further doses of the drug. The body weight of the dams decreased during the period of treatment.3 There was a modest decrease in litter size (-20%) of the MDMA-treated dams.4 The concentration of 5-HT and its metabolite 5-HIAA was decreased by over 65% in the hippocampus and striatum and 40% in the cortex of the dams 1 week after parturition. In contrast, the content of 5-HT and 5-HIAA in the dorsal telencephalon of the pups of the MDMA-treated dams was the same as that seen in tissue from pups born to control animals.5 Administration of MDMA (40 mg kg(-1), s.c.) to adult rats increased thiobarbituric acid reacting substances (TEARS) in cortical tissue 3 h and 6 h later, indicating increased lipid peroxidation. No increase in TEARS was seen in the cortical tissue of 7-10 day neonates injected with this dose of MDMA 3 h or 6 h earlier.6 The data suggest that exposure to MDMA in utero during the maturation phase does not produce damage to 5-HT nerve terminals in the foetal rat brain, in contrast to the damage seen in the brains of the mothers. This may be due to MDMA being metabolized to free radical producing entities in the adult brain but not in the immature brain or, alternatively, to more effective or more active free radical scavenging mechanisms being present in the immature brain.