Teuchert-Noodt G, Dawirs R R
Department of Neuroanatomy, Faculty of Biology, University of Bielefeld, Germany.
Neuropharmacology. 1991 Jul;30(7):733-43. doi: 10.1016/0028-3908(91)90181-a.
Single, intermediate to large doses (6-60 mg/kg) of methamphetamine were applied to study the acute neurotoxic effects in developing male gerbils (up to 24 months). A sensitive silver-staining method was used to analyze the toxicity of methamphetamine by light and electron-microscopy. It was shown that treatment with the drug degraded synaptic components, as well as a small population of neurones in the caudate-putamen complex accompanied by accumulation of lysosomes in fibers and axon terminals. In juveniles, methamphetamine in doses of 25-60 mg/kg, resulted in accumulation of lysosomes, selectively in the prefrontal cortex. In young adults, only about half of these doses were sufficient to produce consistent and/or additional effects in the caudate-putamen complex. When the gerbils grew older than 8 months, treatment with drug led to accumulation of lysosomes, exclusively in the caudate-putamen, with acute doses ranging from 6 to 12 mg/kg. Acute neurotoxicity with methamphetamine has thus been induced by doses, which hitherto have been claimed to produce behavioural sensitization. Since dopamine (DA) seems the most likely transmitter to be affected, age-related differences in methamphetamine-induced neurotoxicity are discussed in relation to the background of developing DA-response systems, which are still changing in pattern during ageing.
应用单剂量、中等至大剂量（6 - 60毫克/千克）的甲基苯丙胺来研究发育中的雄性沙鼠（长达24个月）的急性神经毒性作用。采用一种灵敏的银染方法，通过光学显微镜和电子显微镜分析甲基苯丙胺的毒性。结果显示，药物处理会使突触成分以及尾状核 - 壳核复合体中的少量神经元退化，同时伴有纤维和轴突终末中溶酶体的积累。在幼年沙鼠中，25 - 60毫克/千克剂量的甲基苯丙胺会导致溶酶体选择性地在前额叶皮质积累。在年轻成年沙鼠中，只有约一半的这些剂量足以在尾状核 - 壳核复合体中产生一致和/或额外的效应。当沙鼠长到8个月以上时，用药物处理会导致溶酶体仅在尾状核 - 壳核中积累，急性剂量范围为6至12毫克/千克。因此，甲基苯丙胺的急性神经毒性是由迄今被认为会产生行为敏化的剂量所诱导的。由于多巴胺（DA）似乎是最有可能受影响的神经递质，因此结合发育中的多巴胺反应系统的背景来讨论甲基苯丙胺诱导的神经毒性的年龄相关差异，该系统在衰老过程中模式仍在变化。
