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Development of therapeutic method to suppress drug abuse by suppressing dopamine D1 signal

Research Project

Project/Area Number 16K10197
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Uematsu Ken  久留米大学, 医学部, 非常勤講師 (60441672)

Co-Investigator(Kenkyū-buntansha) 西 昭徳  久留米大学, 医学部, 教授 (50228144)
首藤 隆秀  久留米大学, 医学部, 講師 (70412541)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywordsコカイン / S1Pレセプター / FTY720 / ドーパミンD1シグナル / フィンゴリモド塩酸塩(FTY720) / スフィンゴシン-1-リン酸 / スフィンゴシン-1-リン酸受容体 / 薬物乱用・薬物依存 / フィンゴリモド塩酸塩 / ドーパミンD1シグナル
Outline of Final Research Achievements

In this application study, we focused on the physiologically active lipid, sphingosine-1-phosphate (S1P), and analyzed the central nervous system action in basic researches. The present applicants analyzed the S1P analog molecule, the S1P receptor agonist, and fingolimod hydrochloride [FTY720], using protein phosphorylation as an index at the protein level, and demonstrated that dopamine D1 in medium striatal neurons of the mouse striatum. It was found that the effect of suppressing signal transduction is suppressed. This pharmacological action of FTY720 antagonized the addictive drugs (amphetamine, cocaine, etc.) due to the dopamine activating action, and the group of mice pre-administered with FTY720 was found to have suppressed locomotor hyperactivity due to cocaine administration.

Academic Significance and Societal Importance of the Research Achievements

薬物乱用、薬物依存は大きな社会問題であり社会的損失である。しかし、薬物乱用者、薬物依存者への治療は、精神療法、自助グループへの参加が主体であり、特効薬的治療薬は存在しない。本研究成果で、既に市販されている多発性硬化症治療薬、フィンゴリモド塩酸塩【FTY720】が、薬物依存症治療に応用可能性を持つデータが基礎動物実験で得られた。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (8 results)

All 2019 2018 2017 2016

All Journal Article (1 results) Presentation (5 results) (of which Int'l Joint Research: 2 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] プロテインキナーゼAは代謝型グルタミン酸受容体5を直接リン酸化修飾してその機能が制御される2016

    • Author(s)
      上松 謙
    • Journal Title

      九州神経精神医学

      Volume: 62 Pages: 96-102

    • Related Report
      2016 Research-status Report
  • [Presentation] Fingolimod (FTY720) suppress cocaine-induced hyper locomotion, which attenuate striatal D1-type medium spiny neurons of PKA/DARPP-32 signaling.2018

    • Author(s)
      Ken Uematsu, Takahide Shuto, Yoshihisa Syoji, Naohisa Uchimura, Akinori Nishi
    • Organizer
      Society for Neuroscience
    • Related Report
      2018 Research-status Report
  • [Presentation] Fingolimod attenuates cocaine-induced locomotor activities in vivo by decreasing PKA/DARPP-32 signaling in striatal D1-type medium spiny neurons.(フィンゴリモドは線条体のドーパミンD1タイプ線条体中型有棘神経細胞でPKA/DARPP-32シグナルを抑制してコカインによる過活動性を減弱させる)2017

    • Author(s)
      上松 謙、首藤 隆秀、小路 純央、内村 直尚、西 昭徳
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎ブリックホール
    • Year and Date
      2017-03-15
    • Related Report
      2016 Research-status Report
  • [Presentation] Fingolomod attenuate cocaine induced locomotor activity by decreasing PKA/DARPP32 signaling in striatal D1-type medium spiny neurons.2017

    • Author(s)
      Ken Uematsu, Takahide Shuto, Naohisa Uchimura, Akinori Nishi
    • Organizer
      Neuro Science 2017 ( Washington, DC)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Sphingosine-1-phosphate (S1P) and fingolimod regulate PKA/DARPP-32 signaling in striatal medium spiny neurons via neuronal S1P receptor mechanisms.2016

    • Author(s)
      Ken Uematsu, Takahide Shuto, Yoshihisa Syoji, Naohisa Uchimura, Akinori Nishi
    • Organizer
      Neuro Science 2016
    • Place of Presentation
      Sandiego convention center
    • Year and Date
      2016-11-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Fingolomod regulates PKA/DARPP-32 signaling in striatal medium spiny neurons via neuronal S1P receptor mechanisms (フィンゴリモドはスフィンゴシン-1-リン酸受容体を介して線条体中型有棘細胞のPKA/DARPP-32シグナル伝達を制御する)2016

    • Author(s)
      上松 謙、花田 雄樹、首藤 隆秀、小路 純央、内村 直尚、西 昭徳
    • Organizer
      第39回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-07-20
    • Related Report
      2016 Research-status Report
  • [Patent(Industrial Property Rights)] ドーパミン伝達の抑制剤2019

    • Inventor(s)
      久留米大学
    • Industrial Property Rights Holder
      久留米大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] ドーパミン伝達の抑制剤2019

    • Inventor(s)
      久留米大学
    • Industrial Property Rights Holder
      久留米大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2018 Research-status Report

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Published: 2016-04-21   Modified: 2021-02-19  

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