The neurotoxic effects of 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine on serotonin, dopamine, and GABA-ergic terminals: An in-vitro autoradiographic study in rats
The neurotoxic effects of 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine on serotonin, dopamine, and GABA-ergic terminals: An in-vitro autoradiographic study in rats
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DOI：
10.1016/j.neuro.2004.06.003
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发表时间：
2004-12-01
期刊：
影响因子：
3.4
通讯作者：
Noguchi, KK
中科院分区：
文献类型：
--
作者：
Armstrong, BD;Noguchi, KK
服用 3,4-亚甲二氧基甲基苯丙胺 (MDMA) 后对血清素 (5-HT) 末端的损害已有充分记录，这种毒性被认为与多巴胺释放有关，而多巴胺释放是由药物的 5-HT2A/2C 激动剂作用增强的[Neuro毒理学 19 (3) (1998) 427]。尽管 MDMA 和甲基苯丙胺 (METH) 具有一些相似的多巴胺能活性，但它们的 5-HT 激动特性不同。据推测，对等摩尔剂量的 MDMA 和 METH 对多巴胺和 5-HT 末端产生的毒性的研究应该可以比较这些药物诱导神经毒性的能力。为了测量对大脑的毒性作用，大鼠在皮下植入的渗透微型泵中给予等摩尔剂量的MDMA（40 mg/kg/天）和METH（32 mg/kg/天）为期5天，并使用[H-3]-帕罗西汀、[H-3]-马吲哚、[H-3]-甲基螺哌酮和[H-3]-甲基螺哌隆进行体外放射自显影。 [H-3]-氟硝西泮，在脑切片上进行。结果表明，在前脑区域，包括前扣带回、尾状核、伏隔核和隔膜，METH 对 5-HT 末端的毒性比 MDMA 更强。冰毒对缰核和后压后皮层多巴胺末端的毒性也比摇头丸更大。因此，我们发现连续等摩尔给药后，METH 对突触前和突触后特定大脑区域的 5-HT 和多巴胺末端具有更大的毒性。 (C) 2004 Elsevier Inc. 保留所有权利。
Damage to serotonin (5-HT) terminals following doses of 3,4-methylenedioxymethamphetaniine (MDMA) is well documented, and this toxicity is thought to be related to dopamine release that is potentiated by the 5-HT2A/2C agonist effects of the drug [Neurotoxicology 19 (3) (1998) 427]. Although MDMA and methamphetamine (METH) have some similar dopaminergic activities, they differ in their 5-HT agonistic properties. It is reasoned that the study of the resultant toxicity following equimolar doses of MDMA and METH on both dopamine and 5-HT terminals should offer a comparison of the ability of these drugs to induce neurotoxicity. In order to measure the toxic effects to the brain, rats were given equimolar doses of MDMA (40 mg/kg/day) and METH (32 mg/kg/day) in subcutaneously implanted osmotic minipumps for a period of 5 days, and in-vitro autoradiography using [H-3]-paroxetine, [H-3]-mazindol, [H-3]-methylspiperone, and [H-3]-flunitrazepam, was performed on brain sections. The results showed that METH was more toxic to 5-HT terminals than MDMA in forebrain regions, including the anterior cingulate, caudate nucleus, nucleus accumbens, and septum. METH was also more toxic than MDMA to dopamine terminals in the habenula, and posterior retrosplenial cortex. Therefore, we find that METH was more toxic to 5-HT and dopamine terminals in specific brain regions in both pre and post-synaptic sites following continuous equimolar dosing. (C) 2004 Elsevier Inc. All rights reserved.