Association of Stimulant Use With Dopaminergic Alterations in Users of Cocaine, Amphetamine, or Methamphetamine: A Systematic Review and Meta-analysis.
Association of Stimulant Use With Dopaminergic Alterations in Users of Cocaine, Amphetamine, or Methamphetamine: A Systematic Review and Meta-analysis.
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DOI：
10.1001/jamapsychiatry.2017.0135
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发表时间：
2017-05-01
期刊：
影响因子：
25.8
通讯作者：
Howes OD
中科院分区：
文献类型：
--
作者：
Ashok AH;Mizuno Y;Volkow ND;Howes OD
兴奋剂使用障碍很常见，影响了0.3%至1.1%的人口，每年在全球造成的损失超过850亿美元。目前尚无获得许可的治疗方法。几条线索的证据暗示多巴胺系统在物质使用障碍的病理生理。因此，了解兴奋剂使用者多巴胺功能障碍的本质有可能帮助开发新的治疗方法。全面回顾兴奋剂（可卡因或安非他明/甲基苯丙胺）药物滥用或依赖时多巴胺能改变的体内影像学证据。检索了整个PubMed、EMBASE和PsycINFO数据库，检索了从开始日期到2016年5月14日的研究。共有31项研究利用正电子发射断层扫描或单光子发射计算机断层扫描测量纹状体多巴胺合成或释放，或多巴胺转运体或受体的可用性，比较了519名兴奋剂使用者和512名对照者的多巴胺能测量。从每项研究中提取人口统计学、临床和影像学指标，并在有充分研究的情况下，分别对兴奋剂组合和可卡因和安非他明进行meta分析和敏感性分析。我们确定了可卡因、安非他明和甲基苯丙胺使用者和健康对照者多巴胺释放（通过服用安非他明或哌甲酯后D2/3受体可用性的变化来评估）、转运体和受体可用性的差异。在大多数研究中，禁欲的持续时间从5天到3周不等。纹状体多巴胺释放（兴奋剂联合使用：Hedge’s g= - 0.84；可卡因：- 0.87，均p<0.001）、多巴胺转运体可用性（兴奋剂联合使用：Hedge’s g= - 0.91, p<0.01；安非他命和冰毒：Hedge’s g: - 1.47, p<0.001）和D2/3可用性（兴奋剂联合使用：Hedge’s g= - 0.76；可卡因：- 0.73；安非他命和冰毒：- 0.81，均p<0.001）显著降低。在囊泡单胺转运蛋白、多巴胺合成或D1受体研究中，我们没有发现一致的改变。我们的数据表明，纹状体中多巴胺系统的突触前和突触后两个方面在兴奋剂使用者中都是下调的。我们讨论了这些发现之间的共性和差异，以及与临床前文献的差异，以及它们对未来药物开发的影响。
Stimulant use disorder is common, affecting between 0.3 to 1.1% of the population, and costs over $85 billion per year globally. There are currently no licensed treatments. Several lines of evidence implicate the dopamine system in the pathophysiology of substance use disorder. Thus understanding the nature of dopamine dysfunction seen in stimulant users has the potential to aid the development of new therapeutics. To comprehensively review the in-vivo imaging evidence for dopaminergic alterations in stimulant (cocaine or amphetamine/methamphetamine) drug abuse or dependence. The entire PubMed, EMBASE and PsycINFO databases were searched for studies from inception date to May 14, 2016. A total of 31 studies were identified that compared dopaminergic measures between 519 stimulant users and 512 controls using positron emission tomography or single-photon emission computed tomography to measure striatal dopamine synthesis or release, or dopamine transporter or receptor availability. Demographic, clinical and imaging measures were extracted from each study and meta-analyses and sensitivity analyses were conducted for stimulants combined and cocaine and amphetamines separately where there were sufficient studies. We determined the difference in dopamine release (assessed using change in the D2/3 receptor availability following administration of amphetamine or methylphenidate), transporter and receptor availability in cocaine, amphetamine and methamphetamine users and healthy controls. In majority of the studies the duration of abstinence varied from 5 days to 3 weeks. There was a significant decrease in striatal dopamine release (stimulants combined: Hedge’s g= −0.84; cocaine: −0.87, both p<0.001), dopamine transporter availability (stimulants combined: Hedge’s g= −0.91, p<0.01; amphetamine and methamphetamine: Hedge’s g: −1.47, p<0.001) and D2/3 availability (stimulants combined: Hedge’s g= −0.76; cocaine: −0.73; amphetamine and methamphetamine: −0.81, all p<0.001). We did not find consistent alterations in vesicular monoamine transporter, dopamine synthesis or D1 receptor studies. Our data suggest that both pre and post-synaptic aspects of the dopamine system in the striatum are down-regulated in stimulant users. We discuss the commonality and difference between these findings and the discrepancies with the preclinical literature as well as their implications for future drug development.