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Sex differences in opioid receptor function and brain region-specific processing

Research Project

Project/Area Number 18K15532
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52030:Psychiatry-related
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

MORIYA Yuki  公益財団法人東京都医学総合研究所, 精神行動医学研究分野, 研究員 (50783528)

Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywordsオピオイド受容体 / 雌雄差 / 精神疾患 / 遺伝子改変マウス / 薬物依存 / 抗うつ薬 / chronic stress / behaviors / ストレス感受性 / opioid receptors / ketamine / substance / addiction / abuse / animal models / stress / sex differences / behavioral sensitization / drug addiction / メタンフェタミン (METH) / ケタミン / 行動感作 / 依存症 / 性差 / ストレス / 再燃 / 抗うつ / 行動感作(逆耐性現象) / メタンフェタミン / 覚せい剤 / メタンフェタミン(METH) / オピオイド受容体欠損マウス / ストレス性精神疾患 / 性差医療 / オピオイド受容体ノックダウンマウス / 細胞外モノアミン
Outline of Final Research Achievements

Previous stress research has predominantly focused on males due to the complexity introduced by the female (estrus) cycle, limiting our understanding of stress response, psychiatric disorders, and treatments. To address this gap, this study aimed to elucidate the neuroscientific mechanisms of stress-related psychiatric disorders, considering sex differences, using a mouse model. Specifically, by investigating the role of opioid neurotransmission, which plays a crucial role in stress response, pain, and analgesia, we employed various techniques such as brain microdialysis and behavioral pharmacological tests. This comprehensive analysis provides insights into the sex-specific involvement of the opioid system in stress response. The findings can contribute to the development of drugs and novel therapeutic approaches.

Academic Significance and Societal Importance of the Research Achievements

うつ病をはじめ多くの精神疾患では、発症年齢、治療反応性、進行速度に性差があることを疫学研究は示している。しかし、ストレス感受性や痛み感受性、治療薬の効果や副作用における性差については知られている一方、ストレスが脳機能に与える影響の性差とその分子メカニズムについては不明な点が多い。本研究では、性差の観点からストレスによる精神疾患におけるオピオイド神経伝達系の役割を明らかにすることを目的とした。ストレス応答や疼痛・鎮痛において重要な役割を果たすオピオイド受容体に着目し、行動薬理試験と種々の手法を組み合わせることで、性差を踏まえたストレス応答に対するオピオイド神経系の役割について詳細な解析を行った。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (17 results)

All 2023 2022 2021 2020 2019 2018 Other

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (12 results) (of which Int'l Joint Research: 8 results,  Invited: 1 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Role for μ-opioid receptor in antidepressant effects of δ-opioid receptor agonist KNT-1272023

    • Author(s)
      Moriya Yuki、Kasahara Yoshiyuki、Shimada Masafumi、Sakakibara Yasufumi、Fujii Hideaki、Nagase Hiroshi、Ide Soichiro、Ikeda Kazutaka、Hall F. Scott、Uhl George R.、Sora Ichiro
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 151 Issue: 3 Pages: 135-141

    • DOI

      10.1016/j.jphs.2022.12.008

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Overexpression of tyrosine hydroxylase in dopaminergic neurons increased sensitivity to methamphetamine2023

    • Author(s)
      Nago-Iwashita Yuka、Moriya Yuki、Hara Satoshi、Ogawa Ryohei、Aida Rina、Miyajima Katsuya、Shimura Takenobu、Muramatsu Shin-ichi、Ide Soichiro、Ikeda Kazutaka、Ichinose Hiroshi
    • Journal Title

      Neurochemistry International

      Volume: 164 Pages: 105491-105491

    • DOI

      10.1016/j.neuint.2023.105491

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Repeated methamphetamine treatment increases spine density in the nucleus accumbens of serotonin transporter knockout mice2019

    • Author(s)
      Yoshiyuki Kasahara、Yasufumi Sakakibara、Takashi Hiratsuka、Yuki Moriya、Klaus‐Peter Lesch、F. Scott Hall、George R. Uhl、Ichiro Sora
    • Journal Title

      Neuropsychopharmacology Reports

      Volume: - Issue: 2 Pages: 1-4

    • DOI

      10.1002/npr2.12049

    • NAID

      120006996916

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] A role for the mu opioid receptor in the antidepressant effects of a delta opioid receptor agonist KNT-1272022

    • Author(s)
      Yuki Moriya, Yoshiyuki Kasahara, Masafumi Shimada, Yasufumi Sakakibara, Hideaki Fujii, Hiroshi Nagase, Soichiro Ide, Kazutaka Ikeda, F. Scott Hall, George R. Uhl, Ichiro Sora
    • Organizer
      第34回国際神経精神薬理学会議 (CINP2022)
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] δオピオイド受容体作動薬KNT-127の抗うつ作用におけるμオピオイド受容体の役割の解明2022

    • Author(s)
      Yuki Moriya, Yoshiyuki Kasahara, Masafumi Shimada, Yasufumi Sakakibara, Hideaki Fujii, Hiroshi Nagase, Soichiro Ide, Kazutaka Ikeda, F. Scott Hall, George R. Uhl, Ichiro Sora
    • Organizer
      2022年度文部科学省新学術領域研究 先端モデル動物支援プラットフォーム 若手支援技術講習会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 動物の行動から何が分かるのか ~精神疾患のメカニズムを解明するための行動科学的解析方法~2022

    • Author(s)
      森屋由紀
    • Organizer
      国立大学法人電気通信大学 脳・医工学研究センター(CNBE)の第96回セミナー
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Sex differences in effects of ketamine-induced locomotor activity in socially isolated mice2021

    • Author(s)
      Yuki Moriya, Soichiro Ide, Kazutaka Ikeda
    • Organizer
      AsCNP2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] μオピオイド受容体遺伝子欠損マウスを用いたδオピオイド受容体作動薬の抗うつ効果の検討2021

    • Author(s)
      Yuki Moriya
    • Organizer
      2021年度文部科学省新学術領域研究 先端モデル動物支援プラットフォーム 若手支援技術講習会
    • Related Report
      2021 Research-status Report
  • [Presentation] μ-opioid receptor knockout mice were resistant to relapse to methamphetamine use after periods of abstinence2021

    • Author(s)
      Yuki Moriya, F. Scott Hall, Yoshiyuki Kasahara, Yoko Hagino, Brigitte L. Kieffer, George R. Uhl, Ichiro
    • Organizer
      CINP2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] メタンフェタミン誘発性行動感作におけるセロトニン1B受容体の役割2020

    • Author(s)
      森屋 由紀
    • Organizer
      2020年若手支援技術講習会 FY2020 Technical Training Course for the Youth
    • Related Report
      2020 Research-status Report
  • [Presentation] Role of opioid receptors in behavioral sensitization to methamphetamine2019

    • Author(s)
      Yuki Moriya, F. Scott Hall, Yoshiyuki Kasahara, Yoko Hagino, Brigitte L. Kieffer, George R. Uhl, Ichiro Sora, Kazutaka Ikeda
    • Organizer
      The International Behavioral Neuroscience Society (IBNS)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Opioid system is involved in modulating the development of behavioral sensitization to METH.2019

    • Author(s)
      Yuki Moriya, F. Scott Hall, Yoshiyuki Kasahara, Yoko Hagino, Brigitte L. Kieffer, George R. Uhl, Ichiro Sora, Kazutaka Ikeda
    • Organizer
      The International Narcotics Research Conference (INRC)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Behavioral sensitization and relapse in mu-, delta- and kappa-opioid receptor knockout mice2019

    • Author(s)
      Yuki Moriya, F. Scott Hall, Yoshiyuki Kasahara, Yoko Hagino, Brigitte L. Kieffer, George R. Uhl, Ichiro Sora, Kazutaka Ikeda
    • Organizer
      第6回 アジア神経精神薬理学会大会 (AsCNP2019)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] How social deprivation differentially affects alcohol intake behavior among male and female mice?2018

    • Author(s)
      Yuki Moriya; Yoshiyuki Kasahara; F. Scott Hall; Kazutaka Ikeda; George R. Uhl; Ichiro Sora
    • Organizer
      ISBRA (International Society for Biomedical Research on Alcoholism)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] The role of the serotonin 1B receptor system in the development of methamphetamine-induced sensitization2018

    • Author(s)
      Yuki Moriya; Yoshiyuki Kasahara; Yoko Hagino; F. Scott Hall; Ren; Hen; Kazutaka Ikeda; George R. Uhl; Ichiro Sora
    • Organizer
      The International Behavioral Neuroscience Society (IBNS)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Book] マウス・ラットモデル作製・解析プロフェッショナル2021

    • Author(s)
      先端モデル動物支援プラットフォーム(AdAMS)
    • Total Pages
      320
    • Publisher
      羊土社
    • ISBN
      9784758121125
    • Related Report
      2020 Research-status Report
  • [Remarks] 公益財団法人 東京都医学総合研究所 精神行動医学研究分野 依存性薬物プロジェクト

    • URL

      http://www.igakuken.or.jp/abuse/

    • Related Report
      2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2024-01-30  

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