Ali S F, Newport G D, Scallet A C, Binienda Z, Ferguson S A, Bailey J R, Paule M G, Slikker W
Division of Neurotoxicology, National Center for Toxicological Research, Jefferson, AR 72079-9502.
Neurotoxicol Teratol. 1993 Mar-Apr;15(2):91-6. doi: 10.1016/0892-0362(93)90067-x.
MDMA (3,4-methylenedioxymethamphetamine) has been reported to produce serotonergic depletion in nonhuman primates at doses as low as 2.5 mg/kg (1-2 times the typical human dose). The current study evaluated the dose-response relationships of MDMA (1.25-20.0 mg/kg) using regional concentrations of serotonin (5-HT) and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and home cage behavior as endpoints. Adult female rhesus monkeys (n = 16) were treated orally with 0, 1.25, 2.5, or 20.0 mg/kg MDMA twice daily for 4 consecutive days. Eighteen behaviors were measured in the home cage prior to, during, and after MDMA treatment. One month after the last dose, the animals were sacrificed and brains dissected into several regions for neurochemical analyses. 5-HT and 5-HIAA were analyzed via HPLC/EC. The lower doses of MDMA (1.25 and 2.5 mg/kg) did not significantly alter 5-HT or 5-HIAA concentrations in any brain region except hippocampus in which 5-HT concentrations were decreased after 2.5 mg/kg. MDMA at 20.0 mg/kg significantly decreased 5-HT and 5-HIAA concentrations in several cortical and midbrain structures. However, 5-HT and 5-HIAA concentrations in brain stem and hypothalamus were not significantly altered after any dose of MDMA. Combined with previous data from this laboratory, these results indicate that the decreased concentrations of 5-HT and 5-HIAA in selected brain regions show a selective dose-response relationship for MDMA-induced neurotoxicity as measured by serotonergic depletion in the nonhuman primate.
据报道，摇头丸（3,4－亚甲基二氧甲基苯丙胺）在非人类灵长类动物中，低至2.5毫克/千克（为典型人类剂量的1 - 2倍）的剂量就会导致血清素耗竭。本研究以血清素（5 - HT）及其代谢物5 - 羟吲哚乙酸（5 - HIAA）的区域浓度以及笼内行为为终点，评估了摇头丸（1.25 - 20.0毫克/千克）的剂量反应关系。成年雌性恒河猴（n = 16）连续4天每天口服两次0、1.25、2.5或20.0毫克/千克的摇头丸。在摇头丸治疗前、治疗期间和治疗后，在笼内测量了18种行为。最后一剂给药后一个月，处死动物并将大脑解剖成几个区域进行神经化学分析。通过高效液相色谱/电化学检测法分析5 - HT和5 - HIAA。较低剂量的摇头丸（1.25和2.5毫克/千克）除了在海马体中，2.5毫克/千克剂量后5 - HT浓度降低外，在任何脑区均未显著改变5 - HT或5 - HIAA浓度。20.0毫克/千克的摇头丸显著降低了几个皮质和中脑结构中的5 - HT和5 - HIAA浓度。然而，任何剂量的摇头丸给药后，脑干和下丘脑的5 - HT和5 - HIAA浓度均未显著改变。结合该实验室以前的数据，这些结果表明，在选定脑区中5 - HT和5 - HIAA浓度的降低显示出在非人类灵长类动物中通过血清素耗竭测量的摇头丸诱导神经毒性的选择性剂量反应关系。
