Cadet J L, Brannock C
Molecular Neuropsychiatry Section, NIH/NIDA, Intramural Research Program, Baltimore, MD 21224, USA.
Neurochem Int. 1998 Feb;32(2):117-31. doi: 10.1016/s0197-0186(97)00031-4.
Oxygen is an essential element for normal life. However, reactive oxygen species (ROS) can also participate in deleterious reactions that can affect lipid, protein, and nucleic acid. Normal physiological function thus depends on a balance between these ROS and the scavenging systems that aerobic organisms have developed over millennia. Tilting of that balance towards a pro-oxidant state might result from both endogenous and exogenous causes. In the present paper, we elaborate on the thesis that the neurodegenerative effects of two drugs, namely methamphetamine (METH, ICE) and methylenedioxymethamphetamine (MDMA, Ecstasy) are due to ROS overproduction in monoaminergic systems in the brain. We also discuss the role of oxygen-based species in 6-hydroxydopamine (6-OHDA)-induced nigrostriatal dopaminergic degeneration and in Parkinson's disease. Studies are underway to identify specific cellular and molecular mechanisms that are regulated by oxygen species. These studies promise to further clarify the role of oxidative stress in neurodegeneration and in plastic changes that occur during the administration of addictive agents that affect the brain.
氧气是正常生命活动所必需的元素。然而，活性氧（ROS）也会参与有害反应，影响脂质、蛋白质和核酸。因此，正常生理功能取决于这些活性氧与需氧生物历经数千年发展出的清除系统之间的平衡。这种平衡向促氧化状态倾斜可能由内源性和外源性原因导致。在本文中，我们详细阐述了两种药物，即甲基苯丙胺（METH，冰毒）和亚甲二氧基甲基苯丙胺（MDMA，摇头丸）的神经退行性作用是由于大脑单胺能系统中活性氧过量产生这一论点。我们还讨论了活性氧在6-羟基多巴胺（6-OHDA）诱导的黑质纹状体多巴胺能神经元变性以及帕金森病中的作用。目前正在进行研究以确定受活性氧调节的特定细胞和分子机制。这些研究有望进一步阐明氧化应激在神经退行性变以及在影响大脑的成瘾药物给药过程中发生的可塑性变化中的作用。
