Wilson J M, Kalasinsky K S, Levey A I, Bergeron C, Reiber G, Anthony R M, Schmunk G A, Shannak K, Haycock J W, Kish S J
Human Neurochemical Pathology Laboratory, Clarke Institute of Psychiatry, Toronto, Ontario, Canada.
Nat Med. 1996 Jun;2(6):699-703. doi: 10.1038/nm0696-699.
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 psychostimulant, 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, 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.
甲基苯丙胺是一种在全球范围内被大量滥用的毒品。虽然已有报道称,接受极高剂量这种精神兴奋剂的非人类灵长类动物纹状体中多巴胺及其他多巴胺神经末梢标志物会出现长期耗竭,但关于人类的相关信息却尚无定论。我们发现,慢性甲基苯丙胺使用者死后的纹状体(伏隔核、尾状核、壳核)中,三种多巴胺神经末梢标志物(多巴胺、酪氨酸羟化酶和多巴胺转运体)的水平有所降低。然而,已知在帕金森病中会减少的多巴脱羧酶和囊泡单胺转运体的水平却正常。这表明,在我们研究中的年轻受试者所使用的剂量下,长期接触甲基苯丙胺并不会导致纹状体多巴胺神经末梢的永久性退化。不过,多巴胺减少可能会解释该药物的一些烦躁不安效应,而多巴胺转运体减少则可能为一些甲基苯丙胺使用者出现剂量递增的情况提供了依据。