De Vito M J, Wagner G C
Department of Toxicology, Rutgers, State University, New Brunswick, New Jersey 08903.
Neuropharmacology. 1989 Oct;28(10):1145-50. doi: 10.1016/0028-3908(89)90130-5.
The hypothesis that methamphetamine-induced neuronal damage is mediated by the production of free radicals was evaluated by pretreating rats with either antioxidants or a superoxide dismutase (SOD) inhibitor. It was found that methamphetamine (dose range 6.25-25.0 mg/kg) caused long-lasting depletions of dopamine and serotonin in the striatum and that pretreatment with the antioxidants, ascorbic acid (10-100 mg/kg), ethanol (1 g/kg), mannitol (2 g/kg), or vitamin E (2 g/kg), attenuated these depletions, whereas pretreatment with the superoxide dismutase inhibitor diethyldithiocarbamate (200-400 mg/kg) exacerbated the depletions. The alteration of this effect by four different antioxidants, as well as an inhibitor of superoxidase dismutase, indicated that oxygen-free radicals may have a role in the methamphetamine-induced neurotoxicity.
通过用抗氧化剂或超氧化物歧化酶（SOD）抑制剂预处理大鼠，评估了甲基苯丙胺诱导的神经元损伤由自由基产生介导的假说。结果发现，甲基苯丙胺（剂量范围为6.25 - 25.0 mg/kg）导致纹状体中多巴胺和5-羟色胺的长期耗竭，而用抗氧化剂预处理，如抗坏血酸（10 - 100 mg/kg）、乙醇（1 g/kg）、甘露醇（2 g/kg）或维生素E（2 g/kg），可减轻这些耗竭，而用超氧化物歧化酶抑制剂二乙基二硫代氨基甲酸盐（200 - 400 mg/kg）预处理则会加剧耗竭。四种不同抗氧化剂以及超氧化物歧化酶抑制剂对这种效应的改变表明，氧自由基可能在甲基苯丙胺诱导的神经毒性中起作用。
