Kita T, Takahashi M, Kubo K, Wagner G C, Nakashima T
Department of Pharmacology, Nara Medical University, Kashihara, Japan.
Pharmacol Toxicol. 1999 Sep;85(3):133-7. doi: 10.1111/j.1600-0773.1999.tb00080.x.
Administration of neurotoxic doses of methamphetamine (8 mg/kg, intraperitoneally x 4 times, at 2 hr intervals) caused a significant decrease in dopamine and 3,4-dihydroxyphenylacetic acid and an increase in 3-methoxytyramine levels in the striatum along with a decrease in serotonin and 5-hydroxyindoleacetic acid levels in the striatum and hippocampus. In addition, the methamphetamine treatment caused an increase in rat rectal temperature. Intraventricular injection of salicylate 105 min. after the last injection of methamphetamine produced an increase in 2,3- and 2,5-dihydroxybenzoic acid in the striatum and hippocampus. Moreover, the ratio of 2,3-dihydroxybenzoic acid to salicylate was significantly increased in the striatum, but not in the hippocampus. These results indicate that the hydroxyl radical may play an important role in methamphetamine-induced neurotoxicity in rat striatum and that its formation may be the result of methamphetamine-induced release of dopamine.
给予神经毒性剂量的甲基苯丙胺（8毫克/千克，腹腔注射，共4次，间隔2小时）会导致纹状体中多巴胺和3,4 - 二羟基苯乙酸显著减少，3 - 甲氧基酪胺水平升高，同时纹状体和海马体中的血清素和5 - 羟基吲哚乙酸水平降低。此外，甲基苯丙胺处理会使大鼠直肠温度升高。在最后一次注射甲基苯丙胺105分钟后，脑室内注射水杨酸盐会使纹状体和海马体中的2,3 - 二羟基苯甲酸和2,5 - 二羟基苯甲酸增加。此外，纹状体中2,3 - 二羟基苯甲酸与水杨酸盐的比率显著增加，但海马体中未增加。这些结果表明，羟自由基可能在甲基苯丙胺诱导的大鼠纹状体神经毒性中起重要作用，其形成可能是甲基苯丙胺诱导多巴胺释放的结果。
