Davidson C, Gow A J, Lee T H, Ellinwood E H
Department of Psychiatry, Box 3870, Duke University Medical Center, Durham, NC 27710, USA.
Brain Res Brain Res Rev. 2001 Aug;36(1):1-22. doi: 10.1016/s0165-0173(01)00054-6.
Research into methamphetamine-induced neurotoxicity has experienced a resurgence in recent years. This is due to (1) greater understanding of the mechanisms underlying methamphetamine neurotoxicity, (2) its usefulness as a model for Parkinson's disease and (3) an increased abuse of the substance, especially in the American Mid-West and Japan. It is suggested that the commonly used experimental one-day methamphetamine dosing regimen better models the acute overdose pathologies seen in humans, whereas chronic models are needed to accurately model human long-term abuse. Further, we suggest that these two dosing regimens will result in quite different neurochemical, neuropathological and behavioral outcomes. The relative importance of the dopamine transporter and vesicular monoamine transporter knockout is discussed and insights into oxidative mechanisms are described from observations of nNOS knockout and SOD overexpression. This review not only describes the neuropathologies associated with methamphetamine in rodents, non-human primates and human abusers, but also focuses on the more recent literature associated with reactive oxygen and nitrogen species and their contribution to neuronal death via necrosis and/or apoptosis. The effect of methamphetamine on the mitochondrial membrane potential and electron transport chain and subsequent apoptotic cascades are also emphasized. Finally, we describe potential treatments for methamphetamine abusers with reference to the time after withdrawal. We suggest that potential treatments can be divided into three categories; (1) the prevention of neurotoxicity if recidivism occurs, (2) amelioration of apoptotic cascades that may occur even in the withdrawal period and (3) treatment of the atypical depression associated with withdrawal.
近年来，对甲基苯丙胺所致神经毒性的研究再度兴起。这归因于：（1）对甲基苯丙胺神经毒性潜在机制有了更深入的了解；（2）它作为帕金森病模型的实用性；（3）该物质滥用情况增加，尤其是在美国中西部和日本。有人认为，常用的单日甲基苯丙胺实验给药方案能更好地模拟人类急性过量用药的病理情况，而需要慢性模型来准确模拟人类长期滥用情况。此外，我们认为这两种给药方案会导致截然不同的神经化学、神经病理学和行为学结果。讨论了多巴胺转运体和囊泡单胺转运体基因敲除的相对重要性，并从nNOS基因敲除和超氧化物歧化酶过表达的观察结果中描述了对氧化机制的见解。这篇综述不仅描述了与甲基苯丙胺相关的啮齿动物、非人灵长类动物和人类滥用者的神经病理学，还聚焦于与活性氧和氮物种相关的最新文献及其通过坏死和/或凋亡对神经元死亡的贡献。还强调了甲基苯丙胺对线粒体膜电位和电子传递链以及随后凋亡级联反应的影响。最后，我们参考戒断后的时间描述了对甲基苯丙胺滥用者的潜在治疗方法。我们认为潜在治疗方法可分为三类：（1）预防复吸时的神经毒性；（2）改善即使在戒断期也可能发生的凋亡级联反应；（3）治疗与戒断相关的非典型抑郁症。
