Persistent cognitive and dopamine transporter deficits in abstinent methamphetamine users
Persistent cognitive and dopamine transporter deficits in abstinent methamphetamine users
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DOI：
10.1002/syn.20471
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发表时间：
2008-02-01
期刊：
影响因子：
2.3
通讯作者：
Ricaurte, George A.
中科院分区：
文献类型：
--
作者：
McCann, Una D.;Kuwabara, Hiroto;Ricaurte, George A.
背景：对戒断的甲基苯丙胺（冰毒）使用者的研究表明，脑多巴胺转运体（DAT）结合电位（BP）以及认知和运动缺陷降低，但目前尚不清楚认知缺陷和脑DAT降低是否随着持续戒断而完全逆转，或者冰毒使用者的行为缺陷是否与多巴胺（DA）缺陷有关。这项研究是为了进一步研究甲基苯丙胺滥用后潜在的持续性精神运动缺陷，以及它们与大脑数据可用性的关系，使用定量PET方法与[C-11]WIN 35428进行测量。方法：对22名戒断冰毒使用者和17名健康非冰毒使用者进行心理测试，以验证冰毒使用者在已知涉及DA神经元的神经精神领域（如工作记忆、执行功能、运动功能）中表现出选择性缺陷的假设。一部分受试者也用[C-11]WIN 35428进行了PET扫描。结果：甲基苯丙胺使用者在短期记忆、执行功能和手灵巧性方面有适度的缺陷。探索性相关分析显示，记忆缺陷，而非执行或运动功能的缺陷，与纹状体DAT BR的减少有关。结论：这些结果表明，戒断冰毒使用者的DAT BP与记忆缺陷之间可能存在联系，并支持冰毒对人类中枢DA神经元产生持久影响的观点。由于甲基安非他明也能对5-羟色胺（5-HT）神经元产生毒性作用，因此需要进一步研究大脑5-羟色胺消耗在戒断甲基安非他明使用者认知缺陷中的潜在作用。
Background: Studies in abstinent methamphetamine (METH) users have demonstrated reductions in brain dopamine transporter (DAT) binding potential (BP), as well as cognitive and motor deficits, but it is not yet clear whether cognitive deficits and brain DAT reductions fully reverse with sustained abstinence, or whether behavioral deficits in METH users are related to dopamine (DA) deficits. This study was conducted to further investigate potential persistent psychomotor deficits secondary to METH abuse, and their relationship to brain DAT availability, as measured using quantitative PET methods with [C-11]WIN 35428. Methods: Twenty-two abstinent METH users and 17 healthy non-METH using controls underwent psychometric testing to test the hypothesis that METH users would demonstrate selective deficits in neuropsychiatric domains known to involve DA neurons (e.g., working memory, executive function, motor function). A subset of subjects also underwent PET scanning with [C-11]WIN 35428. Results: METH users were found to have modest deficits in short-term memory, executive function, and manual dexterity. Exploratory correlational analyses revealed that deficits in memory, but not those in executive or motor function, were associated with decreases in striatal DAT BR Conclusions: These results suggest a possible relationship between DAT BP and memory deficits in abstinent METH users, and lend support to the notion that METH produces lasting effects on central DA neurons in humans. As METH can also produce toxic effects on serotonin (5-HT) neurons, further study is needed to address the potential role of brain 5-HT depletion in cognitive deficits in abstinent METH users.