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首页> 外文期刊>Pharmacology and Toxicology: An International Journal >1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine pretreatment attenuates methamphetamine-induced dopamine toxicity.
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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine pretreatment attenuates methamphetamine-induced dopamine toxicity.

机译：1-甲基-4-苯基-1,2,3,6-四氢吡啶预处理可减轻甲基苯丙胺诱导的多巴胺毒性。

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The effects of pretreatment with MPTP (1-methyl4-phenyl-1,2,3,6-tetrahydropyridine) on the acute and long-term effects of methamphetamine on striatal dopamine were evaluated in BALB/c mice. Four subcutaneous injections of a non-toxic dose of MPTP (8 mg/kg, at 2 hr intervals) were followed three days later by a toxic regimen of methamphetamine (four injections of 4 mg/kg, at 2 hr intervals) and mice were sacrificed immediately or three days later. Control mice received saline in place of the MPTP or methamphetamine and mice were observed for acute changes in body temperature, self-injurious behaviour, and striatal dopamine metabolites, or long-term changes in striatal dopamine levels, tyrosine hydroxylase immunoreactivity and glial fibrillary acidic protein. It was observed that pretreatment with MPTP protected mice against the acute increase in body temperature caused by the methamphetamine but, at the same time, delayed the occurrence of self-injurious behaviour following the repeated injections of methamphetamine. Likewise, pretreatment with MPTP attenuated the long-term depletion of striatal dopamine induced by the methamphetamine as well as the large increase in glial fibrillary acidic protein and the reduction in tyrosine hydroxylase immunoreactivity. The MPTP-treatment itself did not alter any of these neurotoxic markers. Finally, the acute decrease in 3,4-dihydroxyphenyacetic acid levels and increased ratio of 3-methoxytyramine/dopamine observed 60 min. after a single injection of methamphetamine (4 mg/kg) were also attenuated in MPTP-treated mice. These results are discussed in the context of the hypothesis that the low-dose treatment with MPTP may modify exchange diffusion across the striatal cell membrane thereby altering the acute and long-lasting effects of methamphetamine.
机译：在BALB / c小鼠中评估了MPTP（1-甲基4-苯基-1,2,3,6-四氢吡啶）预处理对甲基苯丙胺对纹状体多巴胺的急性和长期作用的影响。四天皮下注射无毒剂量的MPTP（8毫克/千克，间隔2小时），三天后进行一次甲基苯丙胺的毒性治疗（四次注射4毫克/千克，间隔2小时），小鼠立即或三天后牺牲。对照小鼠接受盐水代替MPTP或甲基苯丙胺，观察小鼠的体温，自残行为和纹状体多巴胺代谢产物的急性变化，或纹状体多巴胺水平的长期变化，酪氨酸羟化酶免疫反应性和神经胶质纤维酸性蛋白。观察到，用MPTP预处理可保护小鼠免受由甲基苯丙胺引起的体温的急剧升高，但同时，重复注射甲基苯丙胺后，可延迟自残行为的发生。同样，MPTP预处理减弱了由甲基苯丙胺引起的纹状体多巴胺的长期消耗，以及胶质原纤维酸性蛋白的大量增加和酪氨酸羟化酶免疫反应性的降低。 MPTP处理本身不会改变任何这些神经毒性标记。最后，在60分钟内观察到3,4-二羟基苯乙酸水平急剧下降，3-甲氧基酪胺/多巴胺的比例增加。在单次注射甲基苯丙胺（4 mg / kg）后，MPTP处理的小鼠体内的甲基苯丙胺也减弱。在以下假设的背景下讨论了这些结果：MPTP的低剂量治疗可能会改变跨纹状体细胞膜的交换扩散，从而改变甲基苯丙胺的急性和持久作用。

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