Roles of dopamine D5 receptors in the medial prefrontal cortex on the control of impulsive behavior

Research Project

Project/Area Number	21K20856
Research Category	Grant-in-Aid for Research Activity Start-up
Allocation Type	Multi-year Fund
Review Section	0902:General internal medicine and related fields
Research Institution	Hokkaido University
Principal Investigator	Sasamori Hitomi 北海道大学, 医学研究院, 客員研究員 (20911126)
Project Period (FY)	2021-08-30 – 2023-03-31
Project Status	Completed (Fiscal Year 2022)
Budget Amount *help	¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000) Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	衝動性 / ドパミン / 内側前頭前野 / 行動薬理
Outline of Research at the Start	本研究の最終目的は、衝動性制御の脳内メカニズムを明らかにし、衝動性抑制薬開発への糸口を見出すことである。応募者はこれまでにノルアドレナリン再取り込み阻害薬が内側前頭前野腹側部のドパミンD1様受容体(D1 or D5受容体)刺激を介して衝動性を抑制するという一見理解し難い現象を見出してきた。ドパミンD1様受容体にはドパミンD1受容体とドパミンD5受容体がある。ドパミンD5受容体が高次認知機能に果たす役割は不明な部分が多いが、前頭前野においてはドパミンD5受容体が密に発現する。そこで「内側前頭前野のドパミンD5受容体刺激によって衝動性が抑制される」を立てて、その検証を試みる。
Outline of Final Research Achievements	Major psychiatric disorders such as attention-deficit/hyperactivity disorder and schizophrenia are often accompanied by elevated impulsivity. However, anti-impulsive drug treatments are still limited. To explore a novel molecular target, we examined the role of dopamine D5 receptors in impulse control using mice that completely lack D5 receptors (D5KO mice). We also measured spontaneous activity and learning/memory ability because these deficits could confound the assessment of impulsivity. We found small but significant effects of D5 receptor knockout on home cage activity only at specific times of the day. In addition, an analysis using the q-learning model revealed that D5KO mice displayed lower behavioral adjustment after impulsive actions. However, our results also showed that baseline impulsive actions and the effects of an anti-impulsive drug in D5KO mice were comparable to those in wild-type littermates.
Academic Significance and Societal Importance of the Research Achievements	これらの結果は、D5受容体が衝動性制御に必要でないことを示すものであった。また、D5受容体の行動機能を明らかにするためには、時系列で解析することや学習過程の詳細な解析が必要であることが示された。