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Identification of neural substrate for pathological habit

Research Project

Project/Area Number 17K10270
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Psychiatric science
Research InstitutionShowa University

Principal Investigator

TODA SHIGENOBU  昭和大学, 医学部, 准教授 (00323006)

Co-Investigator(Kenkyū-buntansha) 西川 宏美  金沢大学, 医学系, 研究員 (70534155)
Project Period (FY) 2017-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords習慣 / 注意 / 目標指向性行動 / 線条体 / 最初期遺伝子 / 学習記憶 / 依存症 / 強迫性障害
Outline of Final Research Achievements

First, we confirmed that the alteration of immediate early gene expression in the entire rat striatum during an operant training was mainly processed in Dopamine D1-positive medium spiny neurons. We next tried to ease sustained attentional load during a fixed interval schedule of operant training in rats and found this treatment promoted habit formation. Thus, we concluded that sustained attention to measure temporal intervals may suppress habit development. Third, we aimed to reveal the functional significance of c-fos positive neurons in the rat amygdala in behavioral augmentation and habit formation during operant training. A compound that specifically disrupts c-fos positive cells resulted in the attenuation of behavioral augmentation when treated in the central amygdala, whereas it suppressed habit formation when treated in the basolateral amygdala. Therefore, it is suggested that these two amygdala subregions may play distinct roles in operant training.

Academic Significance and Societal Importance of the Research Achievements

行動の過剰な促進化や習慣化は、依存症や強迫性障害、ギャンブル障害など様々な精神疾患で問題となっており、その病態機序の解明と治療法の開発は急務である。本研究の結果、習慣化における持続性注意の意義が明らかとなった。これは注意の持続に障害を有する ADHDなどで不適切な習慣化が起きやすい可能性を示唆する。また、扁桃体での異なる領域が、行動の促進化と習慣化に関して独自に関与することが示唆された。この結果は、行動の促進化と習慣化を個別に制御できる可能性を示唆しており、例えば将来的には習慣化を阻害することなく、不適切な行動の異常促進だけを抑制する治療法の開発につながる可能性がある。

Report

(6 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (19 results)

All 2021 2020 2019 2018 2017 Other

All Int'l Joint Research (3 results) Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (9 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results)

  • [Int'l Joint Research] NIDA(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] NIDA(米国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] NIDA(米国)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Identification of attention-deficit hyperactivity disorder based on the complexity and symmetricity of pupil diameter2021

    • Author(s)
      Nobukawa Sou、Shirama Aya、Takahashi Tetsuya、Takeda Toshinobu、Ohta Haruhisa、Kikuchi Mitsuru、Iwanami Akira、Kato Nobumasa、Toda Shigenobu
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 1-14

    • DOI

      10.1038/s41598-021-88191-x

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Platelet-derived growth factor BB: A potential diagnostic blood biomarker for differentiating bipolar disorder from major depressive disorder.2021

    • Author(s)
      Idemoto K, Ishima T, Niitsu T, Hata T, Yoshida S, Hattori K, Horai T, Otsuka I, Yamamori H, Toda S, Kameno Y, Ota K, Oda Y, Kimura A, Hashimoto T, Mori N, Kikuchi M, Minabe Y, Hashimoto R, Hishimoto A, Nakagome K, Iyo M, Hashimoto K.
    • Journal Title

      J Psychiatr Res

      Volume: 134 Pages: 48-56

    • DOI

      10.1016/j.jpsychires.2020.12.051

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum levels of glial cell line-derived neurotrophic factor as a biomarker for mood disorders and lithium response2021

    • Author(s)
      Keita Idemoto, Tamaki Ishima, Tomihisa Niitsu, Tatsuki Hata, Sumiko Yoshida, Kotaro Hattori, Tadasu Horai, Ikuo Otsuka, Hidenaga Yamamori, Shigenobu Toda etc
    • Journal Title

      Psychiatric Res

      Volume: 301 Pages: 113967-113967

    • DOI

      10.1016/j.psychres.2021.113967

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pupillometric Complexity and Symmetricity Follow Inverted-U Curves Against Baseline Diameter Due to Crossed Locus Coeruleus Projections to the Edinger-Westphal Nucleus2021

    • Author(s)
      Nobukawa Sou、Shirama Aya、Takahashi Tetsuya、Takeda Toshinobu、Ohta Haruhisa、Kikuchi Mitsuru、Iwanami Akira、Kato Nobumasa、Toda Shigenobu
    • Journal Title

      Frontiers in Physiology

      Volume: 12 Pages: 614479-90

    • DOI

      10.3389/fphys.2021.614479

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sustaining temporal attention prevents habit expression during operant learning in rats2020

    • Author(s)
      Lin Ziqiao、Nishikawa Hiromi、Iguchi Yoshio、Iwanami Akira、Kikuchi Mitsuru、Toda Shigenobu
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 10303-10303

    • DOI

      10.1038/s41598-020-67304-y

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Atypical alert state control in adult patients with ADHD: A pupillometry study2020

    • Author(s)
      Shirama Aya、Takeda Toshinobu、Ohta Haruhisa、Iwanami Akira、Toda Shigenobu、Kato Nobumasa
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 12 Pages: e0244662-e0244662

    • DOI

      10.1371/journal.pone.0244662

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 生化学研究の長期展望2017

    • Author(s)
      戸田重誠
    • Journal Title

      精神科

      Volume: 30 Pages: 213-216

    • Related Report
      2017 Research-status Report
  • [Presentation] Pupil Diameter Control Model Focusing on the Left-Right Difference of the Neural Activity Locus Coeruleus of ADHD2021

    • Author(s)
      熊野 開、信川 創、白間 綾、高橋 哲也、戸田 重誠
    • Organizer
      NOLTA/ /2021.12.9
    • Related Report
      2021 Annual Research Report
  • [Presentation] ADHD における瞳孔制御モデルの構築2021

    • Author(s)
      熊野 開、 信川 創、白間 綾、高橋 哲也、戸田 重誠
    • Organizer
      FIT2021(第20 回情報技術科学フォーラム)
    • Related Report
      2021 Annual Research Report
  • [Presentation] 気分障害のバイオマーカーとしての血清中血小板由来増殖因子(PDGF-BB) に関する多施設共同研究2019

    • Author(s)
      井手本啓太、石間環、新津富央、畑達記、小田靖典、木村敦史、亀野陽亮、蓬莱政、山森英長、戸田重誠、菱本明豊、橋本亮太、中込和幸、伊豫雅臣、橋本謙二
    • Organizer
      第16回日本うつ病学会 徳島、2019.7.5
    • Related Report
      2019 Research-status Report
  • [Presentation] Atypical alert state control in adult ADHD : A pupillometry study2019

    • Author(s)
      Aya Shirama, Toshinobu Takeda, Haruhisa Ohta, Shigenobu Toda
    • Organizer
      第49回 日本神経精神薬理学会、福岡、R1.10.12
    • Related Report
      2019 Research-status Report
  • [Presentation] HOW IS A HABIT DEVELOPED OR UNDEVELOPED?: IMPLICATIONS FOR A CRITICAL ROLE OF ATTENTION DURING A GOAL-DIRECTED PROCESS OF OPERANT LEARNING IN RATS.2018

    • Author(s)
      S Toda, Z Lin, H Nishikawa, Y Iguchi, A Iwanami, Y Minabe
    • Organizer
      ISBRA2018京都
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Stage-dependent integration of regulatory processes for the transition from goal-directed to habitual action in striatal direct pathway.2018

    • Author(s)
      Shigenobu Toda
    • Organizer
      第41回日本神経科学学会大会
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Continuous attentional demand may prevent habit formation in rats.2018

    • Author(s)
      Lin Z, Nishikawa H, Iguchi Y, Iwanami, A, Minabe Y, Toda S
    • Organizer
      第41回日本神経科学学会大会
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] The overt and covert interactions between goal-directed behavior and habit2017

    • Author(s)
      S. Toda
    • Organizer
      Invited Seminar, Department of Psychology, University of Sussex, Brighton, UK
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] ラットにおいて習慣化を制御するのは、注意か?予測機能か?2017

    • Author(s)
      戸田重誠
    • Organizer
      第39回日本生物学的精神医学会・第47回日本神経精神薬理学会合同学会
    • Related Report
      2017 Research-status Report
    • Invited

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Published: 2017-04-28   Modified: 2023-01-30  

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