Takahashi Hidehiko, Kato Motoichiro, Takano Harumasa, Arakawa Ryosuke, Okumura Masaki, Otsuka Tatsui, Kodaka Fumitoshi, Hayashi Mika, Okubo Yoshiro, Ito Hiroshi, Suhara Tetsuya
Molecular Imaging Center, Department of Molecular Neuroimaging, National Institute of Radiological Sciences, Inage, Chiba 263-8555, Japan.
J Neurosci. 2008 Nov 12;28(46):12032-8. doi: 10.1523/JNEUROSCI.3446-08.2008.
Dopamine D(1) receptors in the prefrontal cortex (PFC) are important for prefrontal functions, and it is suggested that stimulation of prefrontal D(1) receptors induces an inverted U-shaped response, such that too little or too much D(1) receptor stimulation impairs prefrontal functions. Less is known of the role of D(2) receptors in cognition, but previous studies showed that D(2) receptors in the hippocampus (HPC) might play some roles via HPC-PFC interactions. We measured both D(1) and D(2) receptors in PFC and HPC using positron emission tomography in healthy subjects, with the aim of elucidating how regional D(1) and D(2) receptors are differentially involved in frontal lobe functions and memory. We found an inverted U-shaped relation between prefrontal D(1) receptor binding and Wisconsin Card Sorting Test performance. However, prefrontal D(2) binding has no relation with any neuropsychological measures. Hippocampal D(2) receptor binding showed positive linear correlations not only with memory function but also with frontal lobe functions, but hippocampal D(1) receptor binding had no association with any memory and prefrontal functions. Hippocampal D(2) receptors seem to contribute to local hippocampal functions (long-term memory) and to modulation of brain functions outside HPC ("frontal lobe functions"), which are mainly subserved by PFC, via the HPC-PFC pathway. Our findings suggest that orchestration of prefrontal D(1) receptors and hippocampal D(2) receptors might be necessary for human executive function including working memory.
前额叶皮质（PFC）中的多巴胺D(1)受体对前额叶功能很重要，有研究表明，刺激前额叶D(1)受体会诱发倒U型反应，即D(1)受体刺激过少或过多都会损害前额叶功能。关于D(2)受体在认知中的作用了解较少，但先前的研究表明，海马体（HPC）中的D(2)受体可能通过HPC-PFC相互作用发挥一些作用。我们使用正电子发射断层扫描技术测量了健康受试者PFC和HPC中的D(1)和D(2)受体，目的是阐明区域D(1)和D(2)受体如何不同地参与额叶功能和记忆。我们发现前额叶D(1)受体结合与威斯康星卡片分类测试表现之间存在倒U型关系。然而，前额叶D(2)结合与任何神经心理学测量均无关联。海马体D(2)受体结合不仅与记忆功能呈正线性相关，还与额叶功能呈正线性相关，但海马体D(1)受体结合与任何记忆和前额叶功能均无关联。海马体D(2)受体似乎有助于局部海马体功能（长期记忆），并通过HPC-PFC通路调节HPC以外的脑功能（“额叶功能”），这些功能主要由PFC支持。我们的研究结果表明，前额叶D(1)受体和海马体D(2)受体的协同作用可能是人类包括工作记忆在内的执行功能所必需的。
