Low level of brain dopamine D2 receptors in methamphetamine abusers:: Association with metabolism in the orbitofrontal cortex
Low level of brain dopamine D2 receptors in methamphetamine abusers:: Association with metabolism in the orbitofrontal cortex
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DOI：
10.1176/appi.ajp.158.12.2015
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发表时间：
2001-12-01
影响因子：
17.7
通讯作者：
Pappas, N
中科院分区：
文献类型：
--
作者：
Volkow, ND;Chang, L;Pappas, N
目的：多巴胺在成瘾过程（失控和强迫性药物摄入）中的作用尚不清楚。在药物成瘾受试者中的一致发现是多巴胺D-2受体水平较低。在可卡因滥用者中，低水平的D-2受体与眶额皮质的低水平代谢有关。由于眶额皮质与强迫行为有关，其破坏可能有助于成瘾受试者的强迫性药物摄入。本研究探讨了在甲基苯丙胺滥用者中是否存在类似的相关性。方法：对15名甲基苯丙胺滥用者和20名非药物滥用对照受试者进行了正电子发射断层扫描（PET）和[C-11]雷氯必利研究，以评估多巴胺D-2受体的可用性，并与[F-18]氟脱氧葡萄糖一起评估局部脑葡萄糖代谢，这是脑功能的标志物。结果：甲基苯丙胺滥用者的D-2受体可用性水平显著低于对照组（尾状核差异为16%，壳核差异为10%）。D-2受体的可用性与代谢率在滥用者和比较subjects.Conclusions：较低水平的多巴胺D-2受体的可用性已在可卡因滥用者，酗酒者，海洛因滥用者。这项研究将这一发现扩展到甲基苯丙胺滥用者。多巴胺D-2受体水平与甲基苯丙胺滥用者眶额皮质代谢之间的关联，复制了可卡因滥用者先前的研究结果，表明D-2受体介导的眶额皮质失调可能是药物成瘾受试者失控和强迫性药物摄入的共同机制的基础。
objective: The role of dopamine in the addictive process (loss of control and compulsive drug intake) is poorly understood. A consistent finding in drug-addicted subjects is a lower level of dopamine D-2 receptors. In cocaine abusers, low levels of D-2 receptors are associated with a lower level of metabolism in the orbitofrontal cortex. Because the orbitofrontal cortex is associated with compulsive behaviors, its disruption may contribute to compulsive drug intake in addicted subjects. This study explored whether a similar association occurs in methamphetamine abusers.Method: Fifteen methamphetamine abusers and 20 non-drug-abusing comparison subjects were studied with positron emission tomography (PET) and [C-11]raclopride to assess the availability of dopamine D-2 receptors and with [F-18]fluorodeoxyglucose to assess regional brain glucose metabolism, a marker of brain function.Results: Methamphetamine abusers had a significantly lower level of D-2 receptor availability than comparison subjects (a difference of 16% in the caudate and 10% in the putamen). D-2 receptor availability was associated with metabolic rate in the orbitofrontal cortex in abusers and in comparison subjects.Conclusions: Lower levels of dopamine D-2 receptor availability have been previously reported in cocaine abusers, alcoholics, and heroine abusers. This study extends this finding to methamphetamine abusers. The association between level of dopamine D-2 receptors and metabolism in the orbitofrontal cortex in methamphetamine abusers, which replicates previous findings in cocaine abusers, suggests that D-2 receptor-mediated dysregulation of the orbitofrontal cortex could underlie a common mechanism for loss of control and compulsive drug intake in drug-addicted subjects.