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Elucidation of the mechanism of abnormal motivation in behavioral addiction by 5-HT.

Research Project

Project/Area Number 22K15290
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 47040:Pharmacology-related
Research InstitutionKanazawa University

Principal Investigator

Naoya Nishitani  金沢大学, 薬学系, 助教 (30824792)

Project Period (FY) 2022-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2022: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords行動嗜癖 / ドパミン / 側坐核 / 5-HT / オペラント / ランニングホイール / セロトニン
Outline of Research at the Start

インターネットやゲームなど特定の行動に病的なまでにのめり込む行動嗜癖が社会問題となっている。しかし、行動嗜癖を評価できる実験系や動物モデルは存在せず、基礎研究が不十分なため、病態メカニズムは未解明である。本研究では、行動嗜癖モデルマウスを選別できる新規行動課題を確立し、行動嗜癖で問題となる異常な欲求への関与が疑われる「セロトニンによる脳内報酬系の神経伝達調節の役割」に焦点を当て、神経回路・受容体レベルでの病態メカニズムの解明を目指す。

Outline of Final Research Achievements

The present study used an operant task with a wheel running reward. Fiber photometry recordings of dopamine release and neural activity in the nucleus accumbens (NAc) during the task revealed that DA release increased before motivational behavior and after reward acquisition, and neural activity decreased around motivational behavior and increased after reward acquisition. Inhibition of 5-HT2A and 2C receptors decreased motivation for wheel running but did not affect changes in DA release in the NAc. In addition, we created a mouse model of behavioral addiction based on clinical diagnostic criteria for addiction and found that approximately 35% of the mice were classified as behavioral addiction model mice. Furthermore, it is suggested that activation of cannabinoid CB1 and 5-HT2A receptors may be involved in the formation of behavioral addiction pathology model mice.

Academic Significance and Societal Importance of the Research Achievements

インターネットやゲーム、ギャンブル等に病的にのめり込む行動嗜癖は社会問題となっているが、実験動物を用いた病態メカニズムの研究はほとんど存在しない。本研究では、行動嗜癖の病態メカニズムにおいて、側坐核でのDA遊離変化と神経活動変化が重要であることを解明した。また、5-HT2Aおよび2C受容体の関与も示唆されたが、これはDA遊離へ影響するのではなく、それ以外のメカニズムで作用することが示唆された。最後に、臨床に即した行動嗜癖病態モデルマウスの作製に成功し、病態形成へのCB1および5-HT2A受容体の関与が示唆された。これらの受容体を標的とすることで行動嗜癖の治療法、治療薬開発に繋がると期待される。

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (13 results)

All 2024 2023 2022

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 2 results) Presentation (7 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Social defeat stress enhances the rewarding effects of cocaine through α1A adrenoceptors in the medial prefrontal cortex of mice2024

    • Author(s)
      Saito Atsushi、Murata Haruka、Niitani Kazuhei、Nagasaki Junpei、Otoda Atsuki、Chujo Yusuke、Yanagida Junko、Nishitani Naoya、Deyama Satoshi、Kaneda Katsuyuki
    • Journal Title

      Neuropharmacology

      Volume: 242 Pages: 109757-109757

    • DOI

      10.1016/j.neuropharm.2023.109757

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Varenicline enhances recognition memory via α7 nicotinic acetylcholine receptors in the medial prefrontal cortex in male mice2023

    • Author(s)
      Esaki Hirohito、Deyama Satoshi、Izumi Shoma、Katsura Ayano、Nishikawa Keisuke、Nishitani Naoya、Kaneda Katsuyuki
    • Journal Title

      Neuropharmacology

      Volume: 239 Pages: 109672-109672

    • DOI

      10.1016/j.neuropharm.2023.109672

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Noradrenergic stimulation of α1 adrenoceptors in the medial prefrontal cortex mediates acute stress-induced facilitation of seizures in mice2023

    • Author(s)
      Niitani Kazuhei、Ito Shiho、Wada Shintaro、Izumi Shoma、Nishitani Naoya、Deyama Satoshi、Kaneda Katsuyuki
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 8089-8089

    • DOI

      10.1038/s41598-023-35242-0

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of 5-HT1A receptors in the basolateral amygdala on 3,4-methylenedioxymethamphetamine-induced prosocial effects in mice2023

    • Author(s)
      Hirohito Esaki, Yuki Sasaki, Naoya Nishitani, Hikari Kamada, Satoko Mukai, Yoshitaka Ohshima, Sao Nakada, Xiyan Ni, Satoshi Deyama, Katsuyuki Kaneda
    • Journal Title

      European journal of pharmacology

      Volume: 946 Pages: 175653-175653

    • DOI

      10.1016/j.ejphar.2023.175653

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A spatiotemporal increase of neuronal activity accompanies the motivational effect of wheel running in mice.2022

    • Author(s)
      Zhang T, Nishitani N, Niitani K, Nishida R, Futami Y, Deyama S, Kaneda K
    • Journal Title

      Behavioural Brain Research

      Volume: 432 Pages: 113981-113981

    • DOI

      10.1016/j.bbr.2022.113981

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Median raphe serotonergic neurons projecting to the interpeduncular nucleus control preference and aversion2022

    • Author(s)
      Kawai Hiroyuki、Bouchekioua Youcef、Nishitani Naoya、Niitani Kazuhei、Izumi Shoma、Morishita Hinako、Andoh Chihiro、Nagai Yuma、Koda Masashi、Hagiwara Masako、Toda Koji、Shirakawa Hisashi、Nagayasu Kazuki、Ohmura Yu、Kondo Makoto、Kaneda Katsuyuki、Yoshioka Mitsuhiro、Kaneko Shuji
    • Journal Title

      Nature Communications

      Volume: 13 Issue: 1 Pages: 7708-7708

    • DOI

      10.1038/s41467-022-35346-7

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] ランニングホイール回転行動に対する欲求を指標とした行動嗜癖の病態神経メカニズムの解明2024

    • Author(s)
      小久米 泰祐、谷口 遥海、西谷 直也、金田 勝幸
    • Organizer
      日本薬学会第144年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Nucleus accumbens dopamine receptors modulate motivation for wheel running in mice2024

    • Author(s)
      Naoya Nishitani, Taisuke Kokume, Harumi Taniguchi, Katsuyuki Kaneda
    • Organizer
      CINP2024
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ランニングホイール回転行動への動機づけを指標とした行動嗜癖の神経メカニズムの解明2023

    • Author(s)
      西谷直也、谷口遥海、小久米泰祐、金田勝幸
    • Organizer
      第46回日本神経科学大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] マウスのランニングホイール回転行動を利用した行動嗜癖の病態メカニズムの解明2023

    • Author(s)
      西谷直也、金田勝幸
    • Organizer
      第100回生理学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] ランニングホイール回転運動を報酬とするオペラント課題を用いた行動嗜癖の薬理学的解析2022

    • Author(s)
      西谷直也、金田勝幸
    • Organizer
      BPCNPNPPP4学会合同年会
    • Related Report
      2022 Research-status Report
  • [Presentation] ランニングホイール回転行動に対するモチベーションに関与する脳領域の同定2022

    • Author(s)
      西谷直也、張たん、二井谷和平、西田涼馬、二見優作、出山諭司、金田勝幸
    • Organizer
      BPCNPNPPP4学会合同年会
    • Related Report
      2022 Research-status Report
  • [Presentation] ランニングホイール回転行動に対する動機づけを指標とした行動嗜癖の行動薬理学的解析2022

    • Author(s)
      西谷直也、谷口遥海、小久米泰祐、金田勝幸
    • Organizer
      第96回日本薬理学会年会
    • Related Report
      2022 Research-status Report

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Published: 2022-04-19   Modified: 2025-01-30  

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