Department of Neurosciences, University of Toledo College of Medicine, Toledo, Ohio 43614, USA.
Ann N Y Acad Sci. 2010 Feb;1187:101-21. doi: 10.1111/j.1749-6632.2009.05141.x.
The drugs of abuse, methamphetamine and MDMA, produce long-term decreases in markers of biogenic amine neurotransmission. These decreases have been traditionally linked to nerve terminals and are evident in a variety of species, including rodents, nonhuman primates, and humans. Recent studies indicate that the damage produced by these drugs may be more widespread than originally believed. Changes indicative of damage to cell bodies of biogenic and nonbiogenic amine-containing neurons in several brain areas and endothelial cells that make up the blood-brain barrier have been reported. The processes that mediate this damage involve not only oxidative stress but also include excitotoxic mechanisms, neuroinflammation, the ubiquitin proteasome system, as well as mitochondrial and neurotrophic factor dysfunction. These mechanisms also underlie the toxicity associated with chronic stress and human immunodeficiency virus (HIV) infection, both of which have been shown to augment the toxicity to methamphetamine. Overall, multiple mechanisms are involved and interact to promote neurotoxicity to methamphetamine and MDMA. Moreover, the high coincidence of substituted amphetamine abuse by humans with HIV and/or chronic stress exposure suggests a potential enhanced vulnerability of these individuals to the neurotoxic actions of the amphetamines.
滥用药物，如冰毒和摇头丸，会导致生物胺神经递质传递的标志物长期减少。这些减少传统上与神经末梢有关，在包括啮齿动物、非人类灵长类动物和人类在内的各种物种中都有明显表现。最近的研究表明，这些药物造成的损害可能比最初认为的更为广泛。已经报道了几种脑区的生物胺和非生物胺含能神经元的细胞体以及构成血脑屏障的内皮细胞受损的迹象。介导这种损伤的过程不仅涉及氧化应激，还包括兴奋毒性机制、神经炎症、泛素蛋白酶体系统以及线粒体和神经营养因子功能障碍。这些机制也与慢性应激和人类免疫缺陷病毒 (HIV) 感染相关的毒性有关，这两者都已被证明会增强对冰毒的毒性。总的来说，多种机制参与并相互作用，促进了冰毒和摇头丸的神经毒性。此外，人类滥用苯丙胺类药物与 HIV 和/或慢性应激暴露的高度巧合表明，这些人对苯丙胺类药物的神经毒性作用更容易受到影响。
