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The elucidation of the predictive of psychological changes by chemotherapy mediated the serotonin-kynurenine pathway

Research Project

Project/Area Number 19K07192
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47060:Clinical pharmacy-related
Research InstitutionShujitsu University (2020-2021)
Okayama University (2019)

Principal Investigator

KITAMURA YOSHIHISA  就実大学, 薬学部, 教授 (40423339)

Co-Investigator(Kenkyū-buntansha) 浅沼 幹人  岡山大学, 医歯薬学総合研究科, 教授 (00273970)
Project Period (FY) 2019-04-01 – 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 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords抗がん剤 / 不安 / AC療法 / 神経新生 / セロトニン / キヌレニン / セロトニン1A受容体作用薬 / ドキソルビシン / シクロホスファミド / 化学療法 / セロトニン神経系 / キヌレニン経路 / セロトニン2A受容体 / セロトニン1A受容体 / 5-HT2A受容体 / 5-HT1A受容体 / 精神機能 / ストレス脆弱性
Outline of Research at the Start

実臨床においてがん患者における不安症状、うつ症状などの精神症状についてはよく知られた事実である。この精神機能低下は患者のQOLに悪影響を及ぼしているにも関わらず、適正な薬物治療が行われていない現状である。
一方、申請者らは従来から精神疾患と深く関連している「セロトニン2A受容体機能亢進仮説」の側面からの研究を行い報告してきた。このセロトニン2A受容体機能亢進仮説がさらに進展することにより、抗がん剤により誘発される精神機能低下に対する薬物療法の開発は加速的に進んでいくと考えられる。さらに、キヌレニン関連物質の関与は全く不明であることから、精神機能低下の病態像として新たな理論展開も期待される。

Outline of Final Research Achievements

Serotonin (5-HT) are widely distributed throughout the brain and are involved in the regulation of mood disorders. We demonstrated that the combination of doxorubicin and cyclophosphamide induced anxiety-like behavior. We proposed that the anxiety-like behavior induced by the combination of doxorubicin and cyclophosphamide is mediated by 5-HT2A receptor hyperactivity. And, the combination of doxorubicin and cyclophosphamide induced anxiety-like behavior by 5-HT2A receptor hyperactivity via the phosphorylation of ERK1/2. Furthermore, selective serotonin reuptake inhibitors may attenuate the anxiolytic effects induced by the combination of doxorubicin and cyclophosphamide. Furthermore, a 5-HT1A receptor agonist and a 5-HT2A receptor antagonist ameliorated chemotherapy-induced anxiety-like behavior in rats. Thus, 5-HT2A receptor antagonists or 5-HT1A receptor agonists might be useful for treating chemotherapy-induced anxiety disorders.

Academic Significance and Societal Importance of the Research Achievements

日本人の3人に1人はがんで亡くなる。また、がんと診断を受けた患者の多くは精神的な負担を強いられ、抗がん剤をはじめとした治療の拒否へともつながる。本研究では抗がん剤は不安症状といった精神的な負担を誘発することを明らかにした。その原因は中枢神経系の機能低下によるものであり、ストレスに弱い脳になることを明らかにした。また、治療薬も明らかにし、今後益々増加するがん患者の健全な精神機能の維持に貢献できた。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (4 results)

All 2021 2020 2019

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (2 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Influence of 5-HT2A receptor function on anxiety-like behavior induced by combination treatment with doxorubicin and cyclophosphamide in rats2021

    • Author(s)
      Tabuchi H, Kitamura Y, Ushio S, Kan S, Wada Y, Sumiyoshi Y, Izushi Y, Miyazaki I, Asanuma M, Sendo T.
    • Journal Title

      Psychopharmacology

      Volume: 238 Issue: 12 Pages: 3607-3614

    • DOI

      10.1007/s00213-021-05979-5

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] N-Acetylcysteine Attenuates the Anxiety-Like Behavior and Spatial Cognition Impairment Induced by Doxorubicin and Cyclophosphamide Combination Treatment in Rats2020

    • Author(s)
      Kitamura Yoshihisa、Ushio Soichiro、Sumiyoshi Yusuke、Wada Yudai、Miyazaki Ikuko、Asanuma Masato、Sendo Toshiaki
    • Journal Title

      Pharmacology

      Volume: in press Issue: 5-6 Pages: 1-8

    • DOI

      10.1159/000512117

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Presentation] Involvement of 5-HT1A receptor in the anxiety-like behavior induced by doxorubicin and cyclophosphamide combination treatment in rats.2020

    • Author(s)
      Yoshihisa Kitamura, Soichiro Ushio, Yudai Wada, Toshiaki Sendo
    • Organizer
      2020 Forbidden City International Pharmacist Forum
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effects of serotonin1A receptor agonist on doxorubicin and cyclophosphamide-induced anxiety-like behavior in rats2019

    • Author(s)
      Yoshihisa Kitamura, Yuka Nakamura, Yusuke Sumiyoshi, Nanami Naito, Yudai Wada, Ikuko Miyazaki, Masato Asanuma, Toshiaki Sendo
    • Organizer
      Neuroscience 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2023-01-30  

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