Cognitive function and nigrostriatal markers in abstinent methamphetamine abusers
Cognitive function and nigrostriatal markers in abstinent methamphetamine abusers
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DOI：
10.1007/s00213-006-0330-6
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发表时间：
2006-04-01
影响因子：
3.4
通讯作者：
Schuster, CR
中科院分区：
文献类型：
--
作者：
Johanson, CE;Frey, KA;Schuster, CR
目的：临床前研究证实，甲基苯丙胺(MA)可引起纹状体多巴胺(DA)神经元的长期变化。人类研究表明，类似的影响与运动和认知缺陷有关。这项研究旨在加深我们对人类大脑功能的变化的理解，这些变化可能是在至少3个月的禁欲后长期大剂量使用MA所致。方法：使用单胺转运体神经成像和认知评估，比较戒毒者和对照组的脑功能。纹状体多巴胺转运体(DAT)和囊泡单胺转运体-2(VMAT2)的水平分别用[C-11]哌甲酸甲酯和[C-11]二氢四苯并嗪正电子发射断层扫描测定。通过运动功能、记忆、学习、注意力和执行功能的测试来评估认知功能。结果：在MA滥用者中，纹状体DAT降低约15%，VMAT2降低10%。MA滥用者的表现在正常范围内，但与12项任务中的3项相比，他们的表现更差。结论：未能发现转运蛋白水平和神经认知功能的更多实质性变化可能归因于MA使用者戒断的时间长短(从3个月到10年以上，平均3年)，尽管与戒断时间没有相关性。持续的VMAT2减少支持动物文献，表明MA对黑质纹状体神经末梢有毒性作用。然而，MA对黑质纹状体投射完整性的影响程度足够小，以至于是否有可能出现DA缺乏的临床症状是值得怀疑的。
Objective: Preclinical investigations have established that methamphetamine (MA) produces long-term changes in dopamine (DA) neurons in the striatum. Human studies have suggested similar effects and correlated motor and cognitive deficits. The present study was designed to further our understanding of changes in brain function in humans that might result from chronic high dose use of MA after at least 3 months of abstinence. Method: Brain function in abstinent users was compared to controls using neuroimaging of monoamine transporters and cognitive assessment. Striatal levels of DA transporter (DAT) and vesicular monoamine transporter type-2 (VMAT2) were determined using [C-11]methylphenidate and [C-11]dihydrotetrabenazine positron emission tomography, respectively. Cognitive function was evaluated using tests of motor function, memory, learning, attention, and executive function. Results: Striatal DAT was approximately 15% lower and VMAT2 was 10% lower in MA abusers across striatal subregions. The MA abusers performed within the normal range but performed more poorly compared to controls on three of the 12 tasks. Conclusions: Failure to find more substantial changes in transporter levels and neurocognitive function may be attributed to the length of time that MA users were abstinent (ranging from 3 months to more than 10 years, mean 3 years), although there were no correlations with length of abstinence. Persistent VMAT2 reductions support the animal literature indicating a toxic effect of MA on nigrostriatal nerve terminals. However, the magnitude of the MA effects on nigrostriatal projection integrity is sufficiently small that it is questionable whether clinical signs of DA deficiency are likely to develop.