Commins D L, Vosmer G, Virus R M, Woolverton W L, Schuster C R, Seiden L S
J Pharmacol Exp Ther. 1987 Apr;241(1):338-45.
(+/-)-3,4-Methylenedioxymethylamphetamine (MDMA) was administered s.c. to rats (10, 20 or 40 mg/kg b. wt.) and guinea pigs (20 mg/kg) twice a day for 4 days, 2 weeks before decapitation. Norepinephrine, dopamine and serotonin (5-HT) levels were assayed in the hippocampus, hypothalamus, striatum and neocortex. In rats, MDMA produced dose-dependent reductions in 5-HT in all brain regions examined. The highest dose also reduced norepinephrine and/or dopamine in some regions. The 20-mg/kg dose of MDMA depleted 5-HT in all regions of the guinea pig brain assayed. In both species, repeated administration of 20 mg/kg of MDMA reduced the Vmax but not the Km of 5-HT uptake 2 weeks after administration. A single 40-mg/kg injection of MDMA depleted 5-HT 2 and 8 weeks after administration to rats in all regions of the brain examined except the hypothalamus. Administration of 80 mg/kg of MDMA twice a day for 2 days to rats depleted striatal 5-HT and dopamine. Brain sections from rats injected with MDMA according to this dosage regimen were stained by the Fink-Heimer method. Degenerating axon terminals and cell bodies were observed in the striatum and somatosensory cortex, respectively. These findings suggest that MDMA is toxic to serotonergic and, to a lesser extent, catecholaminergic neurons. Some neurons that do not contain these transmitters (neocortical neurons) are also affected.
将（±）-3,4-亚甲基二氧甲基苯丙胺（摇头丸）以皮下注射的方式给予大鼠（10、20或40毫克/千克体重）和豚鼠（20毫克/千克），每天两次，共4天，在断头前2周进行。检测海马体、下丘脑、纹状体和新皮层中的去甲肾上腺素、多巴胺和5-羟色胺（5-HT）水平。在大鼠中，摇头丸在所有检测的脑区中使5-HT产生剂量依赖性降低。最高剂量在某些区域也降低了去甲肾上腺素和/或多巴胺。20毫克/千克剂量的摇头丸使所检测的豚鼠脑的所有区域中的5-HT耗竭。在两个物种中（±）-3,4-亚甲基二氧甲基苯丙胺（摇头丸），重复给予20毫克/千克的摇头丸在给药2周后降低了5-HT摄取的Vmax但未降低Km。单次注射40毫克/千克的摇头丸在给药后2周和8周使大鼠脑的所有检测区域（下丘脑除外）中的5-HT耗竭。每天两次给予大鼠80毫克/千克的摇头丸，持续2天，使纹状体中的5-HT和多巴胺耗竭。按照此给药方案注射摇头丸的大鼠的脑切片用芬克-海默法染色。分别在纹状体和体感皮层中观察到变性的轴突终末和细胞体。这些发现表明摇头丸对5-羟色胺能神经元有毒性，对儿茶酚胺能神经元的毒性较小。一些不含这些递质的神经元（新皮层神经元）也受到影响。
