Riddle Evan L, Fleckenstein Annette E, Hanson Glen R
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah 84112, USA.
AAPS J. 2006;8(2):E413-8. doi: 10.1007/BF02854914.
Methamphetamine (METH) is a powerful stimulant of abuse with potent addictive and neurotoxic properties. More than 2.5 decades ago, METH-induced damage to dopaminergic neurons was described. Since then, numerous advancements have been made in the search for the underlying mechanisms whereby METH causes these persistent dopaminergic deficits. Although our understanding of these mechanisms remains incomplete, combinations of various complex processes have been described around a central theme involving reactive species, such as reactive oxygen and/or nitrogen species (ROS and RNS, respectively). For example, METH-induced hyperthermia, aberrant dopamine(DA), or glutamate transmission; or mitochondrial disruption leads to the generation of reactive species with neurotoxic consequences. This review will describe the current understanding of how high-dose METH administration leads to the production of these toxic reactive species and consequent permanent dopaminergic deficits.
甲基苯丙胺（METH）是一种具有强大成瘾性和神经毒性的滥用强效兴奋剂。25多年前，就有关于METH对多巴胺能神经元造成损伤的描述。从那时起，在探寻METH导致这些持续性多巴胺能缺陷的潜在机制方面取得了许多进展。尽管我们对这些机制的理解仍不完整，但围绕一个涉及活性物质（如活性氧和/或活性氮，分别为ROS和RNS）的核心主题，已描述了各种复杂过程的组合。例如，METH诱导的体温过高、异常的多巴胺（DA）或谷氨酸传递；或线粒体破坏导致具有神经毒性后果的活性物质生成。本综述将阐述目前对高剂量METH给药如何导致这些有毒活性物质产生以及随之而来的永久性多巴胺能缺陷的理解。
