Involvement of dopamine and noradrenaline signaling mechanisms in depression and schizophrenia.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08083
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Kurume University
• Principal Investigator: Kuroiwa Mahomi 久留米大学, 医学部, 助教 (20585690)
• Co-Investigator(Kenkyū-buntansha): 大西 克典 久留米大学, 医学部, 助教 (10626865) ; 西 昭徳 久留米大学, 医学部, 教授 (50228144) ; 首藤 隆秀 久留米大学, 医学部, 准教授 (70412541)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ドパミン / ノルアドレナリン / うつ病 / 炎症性腸疾患

Outline of Final Research Achievements

We have previously shown that increased expression of hippocampal dentate gyrus-specific dopamine D1 receptors is important for the development of antidepressant effects, but the mechanism is unknown. The present study examined the relationship between monoamine balance in the dentate gyrus and antidepressant effects. The combination of fluoxetine, a selective serotonin reuptake inhibitor, and desipramine, a noradrenaline reuptake inhibitor, enhanced antidepressant effects and increased expression of hippocampal dentate gyrus dopamine D1 receptors. In this study, we also established a mouse model of inflammatory depression and elucidated part of its pathological mechanism. These results are expected to elucidate the mechanism of action of antidepressants with better therapeutic efficacy.

Free Research Field

中枢神経薬理

Academic Significance and Societal Importance of the Research Achievements

海馬歯状回特異的なドパミンD1受容体の発現量増加は抗うつ効果に重要であり、ドパミンD1受容体の増強は抗うつ薬の治療効果を増強する。したがって、ドパミンD1受容体を中心とした抗うつ作用発現の詳細な機序の解明は、うつ病の約3割を占める難治性うつ病の新たな治療法開発への寄与が期待される。また、炎症性腸疾患に併発するうつ病の発症機序を明らかにすることで、従来のうつ病研究とは異なる視点からの病態機序の解明へとつながることが期待される。