Mutual interactions of monoaminergic neurons in stress resilience and sensitivity

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04030
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Niigata University
• Principal Investigator: Nawa Hiroyuki 新潟大学, 脳研究所, 教授 (50183083)
• Co-Investigator(Kenkyū-buntansha): 難波 寿明 新潟大学, 脳研究所, 助教 (90332650) ; 外山 英和 新潟大学, 脳研究所, 特任助教 (40377198)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ドパミン / ストレス / セロトニン / ノルアドレナリン / SSRI

Outline of Final Research Achievements

Pharmacological studies of the serotonin reuptake inhibitor SSRI have given rise to the concept of "serotonin = anti-stress", but the truth is unknown. The purpose of this project is to clarify the role of dopamine and the interaction of three monoamine neural activities in stress sensitivity. After exposure to chronic social defeat stress, the firing activity of three monoaminerigic neurons and the amount of social activity were measured. As a result, a negative correlation with social interaction was found only in the dopaminergic activity. The interventional manipulation of serotoninergic activity and dopaminergic activity with the DREADD method, dopaminerigc activity is more directly involved in the regulation of stress sensitivity and resilience in a downstream of serotonin. Our results suggest that dopamine neuron firing play a direct role in regulating stress sensitivity and resilience.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究から、ラットの慢性的社会敗北ストレス下における3種モノアミン神経発火の相互作用と腹側被蓋野ドパミン神経活動の重要性が示唆された。さらに青斑核ノルアドレナリン神経活動や背側縫線核セロトニン神経活動は、社会行動制御システムにおいてドパミン神経の上流に位置している可能性が仮説された。これらの知見はドパミン神経の新たな神経生理学的役割を明らかにするだけでなく、うつ病の作用機序の解明やより効果的な抗うつ薬の開発に寄与できる可能性がある。