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PET 研究纹状体和纹状体外脑区 D2 受体结合:人类多巴胺能系统的体内生化支持。

PET studies of D2-receptor binding in striatal and extrastriatal brain regions: Biochemical support in vivo for separate dopaminergic systems in humans.

机构信息

Department of Clinical Neuroscience, Stockholm Brain Institute/Karolinska Institute, Stockholm, Sweden.

出版信息

Synapse. 2010 Jun;64(6):478-85. doi: 10.1002/syn.20765.

Abstract

Most molecular imaging studies of the dopamine (DA) system performed to date have focused on the striatum, a region receiving dense dopaminergic innervation. In clinical research on the DA D2-receptor, striatal binding has often been regarded as an index of global DA function, based on the underlying assumption of common regulatory mechanisms for receptor expression across brain regions. Recent data has challenged this view, suggesting differences in genetic regulation between striatal and extrastriatal brain regions. The relationship between binding levels in brain regions has, however, not been directly examined in the same sample. In this study, we searched for interregional correlations between DA D2-receptor availability as determined with Positron Emission Tomography in 16 control subjects. The radioligands [11C]raclopride and [11C]FLB 457 were used for measurements of D2-receptor binding in striatal and extrastriatal regions, respectively. No correlation was observed between D2-receptor availability in striatum and any of the extrastriatal regions, as assessed using both region of interest- and voxel-based analyses. Instead, the pattern of correlations was consistent with the model of separate dopaminergic systems as has been originally observed in rodents. These preliminary results encourage approaches searching for individual patterns of receptor binding across the whole brain volume in clinical studies on the dopamine system.

摘要

迄今为止,大多数关于多巴胺(DA)系统的分子影像学研究都集中在纹状体上,这是一个接受密集多巴胺能神经支配的区域。在 DA D2 受体的临床研究中,基于受体表达的共同调节机制在脑区之间的基本假设,纹状体结合通常被视为整体 DA 功能的指标。最近的数据挑战了这一观点,表明纹状体和纹状体外脑区之间的基因调控存在差异。然而,在同一样本中尚未直接检查脑区之间结合水平的关系。在这项研究中,我们在 16 名对照受试者中搜索了正电子发射断层扫描确定的 DA D2 受体可用性的区域间相关性。放射性配体 [11C]raclopride 和 [11C]FLB 457 分别用于测量纹状体和纹状体外区域的 D2 受体结合。使用感兴趣区域和体素基分析均未观察到纹状体中 D2 受体可用性与任何纹状体外区域之间的相关性。相反,相关性模式与最初在啮齿动物中观察到的独立多巴胺能系统模型一致。这些初步结果鼓励在多巴胺系统的临床研究中寻找整个大脑体积中受体结合的个体模式的方法。

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