Nixdorf W L, Burrows K B, Gudelsky G A, Yamamoto B K
Program in Basic and Clinical Neuroscience, Department of Psychiatry, Case Western Reserve University, Cleveland, USA.
J Neurochem. 2001 Apr;77(2):647-54. doi: 10.1046/j.1471-4159.2001.00262.x.
The acute and long-term effects of the local perfusion of 3,4-methylenedioxymethamphetamine (MDMA) and the interaction with the mitochondrial inhibitor malonate (MAL) were examined in the rat striatum. MDMA, MAL or the combination of MAL with MDMA was reverse dialyzed into the striatum for 8 h via a microdialysis probe while extracellular dopamine (DA) and serotonin (5-HT) were measured. One week later, tissue immediately surrounding the probe was assayed for DA and 5-HT tissue content. Local perfusion of MDMA increased DA and 5-HT release but did not produce long-term depletion of DA or 5-HT in tissue. Malonate also increased both DA and 5-HT release but, in contrast to MDMA, produced only long-term depletion of DA. The combined perfusion of MDMA/MAL synergistically increased the release of DA and 5-HT and produced long-term depletion of both DA and 5-HT in tissue. These results support the conclusion that DA, compared with 5-HT, neurons are more susceptible to mitochondrial inhibition. Moreover, MDMA, which does not normally produce DA depletion in the rat, exacerbated MAL-induced DA depletions. The effect of MDMA in combination with MAL to produce 5-HT depletion suggests a role for bio-energetic stress in MDMA-induced toxicity to 5-HT neurons. Overall, these results highlight the importance of energy balance to the function of DA and 5-HT neurons and to the toxic effects of MDMA.
在大鼠纹状体中研究了3,4-亚甲基二氧基甲基苯丙胺（摇头丸，MDMA）局部灌注的急性和长期影响及其与线粒体抑制剂丙二酸（MAL）的相互作用。通过微透析探针将MDMA、MAL或MAL与MDMA的组合反向透析到纹状体中8小时，同时测量细胞外多巴胺（DA）和5-羟色胺（5-HT）。一周后，检测探针周围组织中的DA和5-HT组织含量。MDMA局部灌注增加了DA和5-HT的释放，但未导致组织中DA或5-HT的长期耗竭。丙二酸也增加了DA和5-HT的释放，但与MDMA不同的是，仅导致DA的长期耗竭。MDMA/MAL联合灌注协同增加了DA和5-HT的释放，并导致组织中DA和5-HT的长期耗竭。这些结果支持以下结论：与5-HT相比，DA能神经元对线粒体抑制更敏感。此外，通常不会在大鼠中导致DA耗竭的MDMA加剧了MAL诱导的DA耗竭。MDMA与MAL联合产生5-HT耗竭的作用表明生物能应激在MDMA诱导的5-HT能神经元毒性中起作用。总体而言，这些结果突出了能量平衡对DA和5-HT能神经元功能以及MDMA毒性作用的重要性。
