Development of three-dimensional atlas of neural transmission and its application for new psychotropic medication

神经传递三维图谱的研制及其在新型精神药物中的应用

• 批准号: 11557070
• 负责人: OKUBO Yoshiro
• 金额: $ 8.64万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11557070/
• 关键词: psychotropic drug; Schizophrenia; PET; MRI; Dopamine; 神経伝達物質; 受容体

The advent of positron emission tomography(PET) neuroreceptor imaging has facilitated an important strategy for elucidating the pathophysiology of neuropsychiatric disorders. PET studies first focused on the striatal dopamine D2 receptor in schizophrenia because of its clinical significance, leading to a revisal of the dopamine hypothesis. Furthermore, empirical data from occupancy measurements have made it possible to directly evaluate the activity of antipsychotic drugs in humans. Recent developments of new radioligands have given rise to new perspectives for understanding actions of psychotroic dugs. Using PET, we aimed to make a three-dimensional atlas of neural transmission and aimed to develop new strategy of psychtropic medication. The follwing results were obtained.1) The use of Computerized Brain Atlas sis of [11C]FLB 457 binding made it possible to build a normal database for the extrastriatal D2 receptors in the living human brain.2) Using [11C]FLB 457, we found reduced D2R binding in the anterior cingulate cortex of patients with schizophrenia, and a significant negative correlation between D2R binding and the positive symptom score on BPRS. These findings suggest that alterations in D2R function in the extrastriatal region may underlie the positive symptoms of schizophrenia.3) D2 receptor occupancy with risperidone in the limbic-cortical regions was similar to that of previous reports regarding the striatum, and it would be comparable to that of typical antipsychotics.

正电子发射断层扫描（PET）神经受体成像的出现促进了阐明神经精神疾病的病理生理学的重要策略。PET研究首先关注精神分裂症患者的纹状体多巴胺D2受体，因为它具有临床意义，导致多巴胺假说的修订。此外，来自占用测量的经验数据使得直接评估抗精神病药物在人体中的活性成为可能。新的放射性配体的最新发展引起了新的观点来理解精神药物的作用。本研究旨在利用正电子发射断层扫描技术，建立神经传导的三维图谱，为精神药物治疗提供新的思路。结果表明：1）应用脑图谱分析[11 C]FLB 457结合，建立了正常人脑纹状体外D2受体的数据库; 2）应用[11 C]FLB 457，我们发现精神分裂症患者前扣带皮层D2 R结合减少，D2 R结合与BPRS阳性症状评分呈显著负相关。这些结果表明，纹状体外区D2受体功能的改变可能是精神分裂症阳性症状的基础。3）利培酮在边缘皮质区的D2受体结合率与先前关于纹状体的报道相似，并且与典型的抗精神病药物相当。

项目成果

Suhara T, Okubo Y, Yasuno F, Sudo Y, Inoue M: "Decreased dopamine D2 receptor binding in the anterior cingulate cortex in schizophrenia"Arch Gen Psychiatry. 59. 25-30 (2002)

Suhara T、Okubo Y、Yasuno F、Sudo Y、Inoue M：“精神分裂症中前扣带皮层多巴胺 D2 受体结合减少”Arch Gen Psychiatry。

Okubo Y, Olsson H, Ito H, Lofti M, Suhara T, Halldin C, Farde L: "PET mapping of extrastriatal D2-like dopamine receptors in the human brain using an anatomic standardization technique and [11C]FLB 457"Neuroimage. 10. 666-74 (1999)

Okubo Y、Olsson H、Ito H、Lofti M、Suhara T、Halldin C、Farde L：“使用解剖标准化技术和 [11C]FLB 457 对人脑中纹状体外 D2 样多巴胺受体进行 PET 绘图”神经图像。

Yasuno F, Suhara T, Okubo Y, Sudo Y, Inoue M, Ichimiya T, Tanada S: "Dose relationship of limbic-cortical D2-dopamine receptor occupancy with risperidone."Psychopharmacology.. 154. 112-114 (2001)

Yasuno F、Suhara T、Okubo Y、Sudo Y、Inoue M、Ichimiya T、Tanada S：“边缘皮质 D2-多巴胺受体占用与利培酮的剂量关系。”精神药理学.. 154. 112-114 (2001)

Suhara T, Yasuno F, Sudo Y, Yamamotom M, Inoue M, Okubo Y, Suzuki K: "Dopamine D2 receptors in the insular cortex and the personality trait of novelty seeking"Neuroimage. 13. 891-895 (2001)

Suhara T、Yasuno F、Sudo Y、Yamamotom M、Inoue M、Okubo Y、Suzuki K：“岛叶皮质中的多巴胺 D2 受体与寻求新奇的人格特质”神经影像。

Saijo,T.,Abe T.,Someya Y.,Sassa T.,Okubo Y. et al.: "Ten year progressive ventricular enlargement in schizophrenia : An MRI morphometrical study."Psychiatry and Clinical Neuroscience. 55. 41-47 (2001)

Saijo,T.,Abe T.,Someya Y.,Sassa T.,Okubo Y.等人：“精神分裂症十年进行性心室扩大：MRI 形态测量研究。”精神病学和临床神经科学。