Mutual interactions of monoaminergic neurons in stress resilience and sensitivity

• 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
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000); Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2017: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
• Keywords: ドパミン / ストレス / セロトニン / ノルアドレナリン / SSRI / 薬理遺伝学 / 社会ストレス / モノアミン / 社会性 / ＳＳＲＩ / 中脳 / ＤＲＥＡＤＤ / ユニット記録 / 行動

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.

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。

Research Products

• [Journal Article] The dual role of dopamine in the modulation of information processing in the prefrontal cortex underlying social behavior (2022)
  • Author(s): Sotoyama Hidekazu、Inaba Hiroyoshi、Iwakura Yuriko、Namba Hisaaki、Takei Nobuyuki、Sasaoka Toshikuni、Nawa Hiroyuki
  • Journal Title: The FASEB Journal Volume: 36 Issue: 2
  • DOI: 10.1096/fj.202101637r
  • Peer Reviewed / Open Access
• [Journal Article] 増大特集 脳とからだ Ⅳ.内分泌系と脳の相互作用 慢性ストレス負荷と抗うつ剤による脳内モノアミン神経活動のバランス制御 (2021)
  • Author(s): 那波宏之、鬼川真紀、難波寿明、外山英和
  • Journal Title: 生体の科学 Volume: 72 Issue: 5 Pages: 497-500
  • DOI: 10.11477/mf.2425201425
  • ISSN: 0370-9531, 1883-5503
  • Year and Date: 2021-10-15
• [Journal Article] Post-pubertal difference in nigral dopaminergic cells firing in the schizophrenia model prepared by perinatal challenges of a cytokine, EGF (2020)
  • Author(s): Namba H, Nawa H
  • Journal Title: Neuroscience Volume: 未定
  • Peer Reviewed
• [Presentation] Persistent hyper-active VTA dopamine neurons lead to social deficits (2019)
  • Author(s): 外山英和、那波宏之
  • Organizer: NEURO2019
• [Presentation] Interaction of three monoaminergic neurons in social stress responses (2019)
  • Author(s): 鬼川真季,、外山英和、難波寿明、 那波宏之
  • Organizer: NEURO2019
• [Presentation] ネズミも精神病にかかる？；統合失調症と動物モデル (2018)
  • Author(s): 那波宏之
  • Organizer: 第１０回脳科学クラスター・ミニリトリート（徳島大学）
  • Invited
• [Presentation] Neuropathologic implication of pallidal hyperactivity in the auditory abnormality of schizophrenia animal models (2017)
  • Author(s): Hiroyuki Nawa
  • Organizer: The 13th World Congress of Biological Psychiatry
  • Int'l Joint Research / Invited