Striatal dopamine nerve terminal markers in human, chronic methamphetamine users
Striatal dopamine nerve terminal markers in human, chronic methamphetamine users
复制标题
DOI：
10.1038/nm0696-699
复制
发表时间：
1996-06-01
期刊：
影响因子：
82.9
通讯作者：
Kish, SJ
中科院分区：
文献类型：
--
作者：
Wilson, JM;Kalasinsky, KS;Kish, SJ
甲基苯丙胺是一种在世界范围内滥用严重的药物。尽管已经报道了在接受非常高剂量的精神刺激剂的非人灵长类动物的纹状体中多巴胺和其他多巴胺神经末梢标记物的长期消耗（1-3），但是没有关于人类的信息。我们发现三个多巴胺神经末梢标记物（多巴胺，酪氨酸羟化酶和多巴胺转运蛋白）的水平降低，在死后的纹状体（神经核，尾状核，壳核）的慢性甲基苯丙胺用户。然而，多巴脱羧酶和囊泡单胺转运蛋白的水平（已知在帕金森病中降低）是正常的（4，5）。这表明，在我们研究中年轻受试者使用的剂量下，长期接触甲基苯丙胺不会导致纹状体多巴胺神经末梢永久变性。然而，多巴胺的减少可能解释了药物的一些烦躁效应，而多巴胺转运蛋白的减少可能为一些甲基苯丙胺使用者的剂量递增提供了依据。
Methamphetamine is a drug that is significantly abused worldwide. Although long-lasting depletion of dopamine and other dopamine nerve terminal markers has been reported in striatum of nonhuman primates receiving very high doses of the psychostimuiant(1-3), no information is available for humans. We found reduced levels of three dopamine nerve terminal markers (dopamine, tyrosine hydroxylase and the dopamine transporter) in post-mortem striatum (nucleus accumbens, caudate, putamen) of chronic methamphetamine users. However, levels of DOPA decarboxylase and the vesicular monoamine transporter, known to be reduced in Parkinson's disease(4,5), were normal. This suggests that chronic exposure to methamphetamine does not cause permanent degeneration of striatal dopamine nerve terminals at the doses used by the young subjects in our study. However, the dopamine reduction might explain some of the dysphoric effects of the drug, whereas the decreased dopamine transporter could provide the basis for dose escalation occurring in some methamphetamine users.