Takahashi Hidehiko
Department of Psychiatry, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
J Physiol Paris. 2013 Dec;107(6):503-9. doi: 10.1016/j.jphysparis.2013.07.001. Epub 2013 Jul 12.
The role of prefrontal dopamine D1 receptors in prefrontal cortex (PFC) functions, including working memory, is widely investigated. However, human (healthy volunteers and schizophrenia patients) positron emission tomography (PET) studies about the relationship between prefrontal D1 receptors and PFC functions are somewhat inconsistent. We argued that several factors including an inverted U-shaped relationship between prefrontal D1 receptors and PFC functions might be responsible for these inconsistencies. In contrast to D1 receptors, relatively less attention has been paid to the role of D2 receptors in PFC functions. Several animal and human pharmacological studies have reported that the systemic administration of D2 receptor agonist/antagonist modulates PFC functions, although those studies do not tell us which region(s) is responsible for the effect. Furthermore, while prefrontal D1 receptors are primarily involved in working memory, other PFC functions such as set-shifting seem to be differentially modulated by dopamine. PET studies of extrastriatal D2 receptors including ours suggested that orchestration of prefrontal dopamine transmission and hippocampal dopamine transmission might be necessary for a broad range of normal PFC functions. In order to understand the complex effects of dopamine signaling on PFC functions, measuring a single index related to basic dopamine tone is not sufficient. For a better understanding of the meanings of PET indices related to neurotransmitters, comprehensive information (presynaptic, postsynaptic, and beyond receptor signaling) will be required. Still, an interdisciplinary approach combining molecular imaging techniques with cognitive neuroscience and clinical psychiatry will provide new perspectives for understanding the neurobiology of neuropsychiatric disorders and their innovative drug developments.
前额叶多巴胺D1受体在包括工作记忆在内的前额叶皮质（PFC）功能中的作用已得到广泛研究。然而，关于前额叶D1受体与PFC功能之间关系的人体（健康志愿者和精神分裂症患者）正电子发射断层扫描（PET）研究结果却有些不一致。我们认为，包括前额叶D1受体与PFC功能之间呈倒U形关系在内的几个因素可能导致了这些不一致。与D1受体相比，D2受体在PFC功能中的作用受到的关注相对较少。一些动物和人体药理学研究报告称，全身给予D2受体激动剂/拮抗剂可调节PFC功能，尽管这些研究并未告诉我们是哪个区域产生了这种作用。此外，虽然前额叶D1受体主要参与工作记忆，但多巴胺对其他PFC功能（如定势转换）的调节似乎存在差异。包括我们的研究在内的纹状体以外D2受体的PET研究表明，前额叶多巴胺传递和海马多巴胺传递的协同作用可能是广泛的正常PFC功能所必需的。为了理解多巴胺信号对PFC功能的复杂影响，仅测量与基本多巴胺水平相关的单一指标是不够的。为了更好地理解与神经递质相关的PET指标的意义，需要综合信息（突触前、突触后以及受体信号以外的信息）。尽管如此，将分子成像技术与认知神经科学和临床精神病学相结合的跨学科方法将为理解神经精神疾病的神经生物学及其创新药物研发提供新的视角。
