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Verification of the importance of central FFAR1 system in nociceptive and emotional behaviors in mice

Research Project

Project/Area Number 16K10792
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurosurgery
Research InstitutionKagoshima University

Principal Investigator

OYOSHI Tatsuki  鹿児島大学, 医歯学域附属病院, 講師 (80315407)

Co-Investigator(Kenkyū-buntansha) 有田 和徳  鹿児島大学, 医歯学総合研究科, 客員研究員 (90212646)
宮田 篤郎  鹿児島大学, 医歯学域医学系, 教授 (60183969)
栗原 崇  鹿児島大学, 医歯学域医学系, 准教授 (60282745)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
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)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsFFAR1 / GPR40 / コカイン / 不安様行動 / セロトニン / in vivo マイクロダイアリシス法 / うつ病 / 炎症性疼痛 / 神経障害性疼痛 / FFAR1 / 内因性疼痛抑制機構 / 脳内モノアミン系 / 疼痛・情動行動
Outline of Final Research Achievements

The free fatty acid receptor 1 (FFAR1) is suggested to function as a G protein-coupled receptor for medium- to long-chain FFAs. Since the role of central FFAR1 has been largely unclarified, we examined the functional role of FFAR1 in the control of striatal monoamines release and cocaine-induced locomotor activity in this study.
Acute administration of cocaine enhanced locomotor activity in both FFAR1 wild-type (+/+) and knockout (-/-) mice, but the magnitude of enhancement was significantly reduced in -/- mice. Microdialysis studies revealed that the basal level of dopamine was significantly elevated, while the serotonin (5-HT) level was tended to be reduced in -/- mice. Moreover, local application of a FFAR1 agonist, GW9508, markedly augmented the 5-HT release in +/+ mice, but the enhanced release was lost in -/- mice. These results suggest that FFAR1 has a facilitatory role in striatal 5-HT release, which might potentiate cocaine-induced locomotor activity.

Academic Significance and Societal Importance of the Research Achievements

中枢神経系におけるFFAR1の機能に関しては未だ不明な点が多い中、本研究は、コカイン投与による移所運動活性亢進における線条体FFAR1の機能的関与(セロトニン放出促進)を示唆した。本結果は、現在進行している「依存性薬物による行動変化におけるFFAR1の機能的関与」に関する研究を推進するきっかけとなった。
また、FFAR1作動薬が脳内セロトニン遊離に関与することから、FFAR1はうつ・不安様行動にも何らかの機能的役割を持つことが推察され、実際、疼痛などのストレス刺激に伴う情動行動変化に重要な役割を持つことが明らかになりつつある。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (13 results)

All 2018 2017 2016

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (8 results)

  • [Journal Article] Acute painful autoimmune neuropathy: A variant of Guillain-Barré syndrome.2018

    • Author(s)
      Yuki N, Chan AC, Wong AHY, Inoue T, Yokai M, Kurihara T, Devaux JJ, Wilder-Smith E.
    • Journal Title

      Muscle & Nerve

      Volume: 57(2) Issue: 2 Pages: 320-324

    • DOI

      10.1002/mus.25738

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] In silico screening identified novel small-molecule antagonists of PAC1 receptor.2018

    • Author(s)
      Takasaki I, Watanabe A, Yokai M, Watanabe Y, Hayakawa, D, Nagashima, R, Fukuchi, M, Okada, T, Toyooka, N, Miyata, A, Gouda H, Kurihara T.
    • Journal Title

      J. Pharmacol. Exp. Ther.

      Volume: - Issue: 1 Pages: 1-8

    • DOI

      10.1124/jpet.117.245415

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dysfunctional GPR40/FFAR1 signaling exacerbates pain behavior in mice.2017

    • Author(s)
      Nakamoto K, Aizawa F, Miyagi K, Yamashita T, Mankura M, Koyama Y, Kasuya F, Hirasawa A, Kurihara T, Miyata A, Tokuyama S.
    • Journal Title

      PLoS One

      Volume: 12(7) Issue: 7 Pages: e0180610-e0180610

    • DOI

      10.1371/journal.pone.0180610

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Deletion of GPR40/FFAR1 Signaling Damages Maternal Care and Emotional Function in Female Mice2017

    • Author(s)
      Aizawa F, Ogaki Y, Kyoya N, Nishinaka T, Nakamoto K, Kurihara T, Hirasawa A, Miyata A, Tokuyama S.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 40 Issue: 8 Pages: 1255-1259

    • DOI

      10.1248/bpb.b17-00082

    • NAID

      130005876328

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] GPR40/FFAR1 deficient mice increase noradrenaline levels in the brain and exhibit abnormal behavior2016

    • Author(s)
      Aizawa F, Nishinaka T, Yamashita T, Nakamoto K, Kurihara T, Hirasawa A, Kasuya F, Miyata A, Tokuyama S.
    • Journal Title

      J Pharmacol Sci.

      Volume: 132 Issue: 4 Pages: 249-254

    • DOI

      10.1016/j.jphs.2016.09.007

    • NAID

      120005997894

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] FFAR1/GPR40は疼痛遷延化に伴う情動行動変化に関与する2018

    • Author(s)
      水沼亮太、栗原 崇、神戸悠輝、平澤 明、中本賀寿夫、大吉達樹、徳山尚吾、有田和徳、宮田篤郎
    • Organizer
      第138回日本薬理学会関東部会
    • Related Report
      2017 Research-status Report
  • [Presentation] FFAR1ノックアウトマウスはコカイン誘発移所運動活性が減弱する2017

    • Author(s)
      貞村祐子、栗原 崇、水沼亮太、神戸悠輝、鮫島芳宗、平澤 明、中本賀寿夫、大吉達樹、徳山尚吾、有田和徳、宮田篤郎
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎ブリックホール・長崎新聞文化ホールアストピア(長崎県長崎市)
    • Year and Date
      2017-03-15
    • Related Report
      2016 Research-status Report
  • [Presentation] GPR40/FFAR1の内因性疼痛抑制機構への関与2017

    • Author(s)
      水沼亮太、栗原 崇、千々和可怜、用皆正文、神戸悠輝、平澤 明、中本賀寿夫、徳山尚吾、宮田篤郎
    • Organizer
      第9回 鹿児島神経科学研究会
    • Place of Presentation
      鹿児島大学郡元キャンパス(鹿児島県鹿児島市)
    • Year and Date
      2017-02-18
    • Related Report
      2016 Research-status Report
  • [Presentation] GPR40/FFAR1の内因性疼痛抑制機構への関与2017

    • Author(s)
      水沼亮太、栗原 崇、千々和可怜、用皆正文、神戸悠輝、平澤 明、中本賀寿夫、徳山尚吾、宮田篤郎
    • Organizer
      第10回 桜ヶ丘地区(基礎系)研究発表会
    • Place of Presentation
      鶴陵会館(鹿児島県鹿児島市)
    • Year and Date
      2017-02-02
    • Related Report
      2016 Research-status Report
  • [Presentation] GPR40/FFAR1は内因性疼痛抑制機構に関与する2017

    • Author(s)
      栗原 崇,千々和可怜,用皆正文,水沼亮太,神戸悠輝,平澤 明,中本賀寿夫,徳山尚吾,宮田篤郎
    • Organizer
      生理研研究会 痛み研究会2016
    • Place of Presentation
      自然科学研究機構岡崎コンファレスセンター(愛知県岡崎市)
    • Year and Date
      2017-01-30
    • Related Report
      2016 Research-status Report
  • [Presentation] GPR40/FFAR1は慢性疼痛に伴ううつ病に関与するか?2017

    • Author(s)
      水沼亮太、栗原 崇、神戸悠輝、平澤明、中本賀寿夫、大吉達樹、徳山尚吾、有田和徳、宮田篤郎
    • Organizer
      第70回日本薬理学会西南部会
    • Related Report
      2017 Research-status Report
  • [Presentation] GPR40/FFAR1欠損マウスはコカイン誘発移所運動活性亢進効果が減弱している2017

    • Author(s)
      貞村祐子、栗原 崇、水沼亮太、神戸悠輝、平澤明、中本賀寿夫、大吉達樹、徳山尚吾、有田和徳、宮田篤郎
    • Organizer
      第70回日本薬理学会西南部会
    • Related Report
      2017 Research-status Report
  • [Presentation] FFAR1は内因性疼痛抑制系制御に関与するか?2016

    • Author(s)
      千々和可怜、栗原 崇、用皆正文、水沼亮太、鮫島芳宗、平澤 明、中本賀寿夫、徳山尚吾、宮田篤郎.
    • Organizer
      第69回日本薬理学会西南部会
    • Place of Presentation
      松山大学(愛媛県松山市)
    • Year and Date
      2016-11-26
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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