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Role of PDEs in antipsychotic effects in hippocampal dentate gyrus.

Research Project

Project/Area Number 26860951
Research Category

Grant-in-Aid for Young Scientists (B)

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

Principal Investigator

Kuroiwa Mahomi  久留米大学, 医学部, 助教 (20585690)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsホスホジエステラーゼ / 海馬歯状回 / ドーパミン / 抗うつ薬 / うつ病 / 統合失調症
Outline of Final Research Achievements

Male DISC1-DN-Tg-PrP and their male littermate Wild-type mice were group-housed or isolated from 5 weeks of age. After the isolation stress, the PDE functions were alterd in the nucleus accumbens and in the striatum. In addition, the same result was suggested in the hippocampal dentate gyrus.
Furthermore, we observed that chronic treatment of C57BL/6 mice with fluoxetine induced the expression of D1 receptors in granule cells. The high expression of D1 receptors resulted in activation of cAMP/PKA signaling in the dentate gyrus. In behavioral studies, D1 receptor agonism enhanced antidepressant action of fluoxetine in mice subjected to chronic restraint stress. Thus, D1 receptors in granule cells, induced by chronic antidepressants, enhance antidepressant effects under stressed conditions. Dopamine D1 receptors may be a therapeutic target of depression.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (16 results)

All 2016 2015 2014

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (15 results) (of which Int'l Joint Research: 4 results)

  • [Journal Article] Chronic Fluoxetine Induces the Enlargement of Perforant Path-Granule Cell Synapses in the Mouse Dentate Gyrus.2016

    • Author(s)
      Kitahara Y, Ohta K, Hasuo H, Shuto T, Kuroiwa M, Sotogaku N, Togo A, Nakamura K, Nishi A
    • Journal Title

      PLos One

      Volume: 11(1) Issue: 1 Pages: e0147307-e0147307

    • DOI

      10.1371/journal.pone.0147307

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 気分制御に関与する蛋白p11は報酬関連ドーパミン神経応答に必要である2016

    • Author(s)
      花田 雄樹、河原 幸江、大西 克典、首藤 隆秀、黒岩 真帆美、外角 直樹、西  昭徳
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-03-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] Social Isolated DISC1 Mutant Mice Displayed High Sensitivity to Chronic Cocaine Exposure and Rolipram Treatment2015

    • Author(s)
      Hikida T, Morita M, Kuroiwa M, Macpherson T, Itou T, Shuto T, Sotogaku N, Niwa M, Sawa A, Nishi A
    • Organizer
      54th American College of Neuropsychopharmacology (ACNP)
    • Place of Presentation
      Hollywood (USA)
    • Year and Date
      2015-12-06
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Chronic treatment with antidepressants enhances dopamine D1 receptor signaling in the hippocampal dentate gyrus2015

    • Author(s)
      Kuroiwa M, Shuto T, Sotogaku N, Oh YS, Nishi A
    • Organizer
      Annual Meeting of Society for Neuroscience (SFN)
    • Place of Presentation
      Chicago (USA)
    • Year and Date
      2015-10-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Dopamine D1 receptor activation enhances antidepressant effects of SSRI in a mouse model of depression2015

    • Author(s)
      Shuto T, Kuroiwa M, Sotogaku N, Nishi A
    • Organizer
      Annual Meeting of Society for Neuroscience (SFN)
    • Place of Presentation
      Chicago (USA)
    • Year and Date
      2015-10-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] DISC1マウスの隔離飼育に対するドパミンシグナル応答:ホスホジエステラーゼの役割2015

    • Author(s)
      黒岩 真帆美、首藤 隆秀、外角 直樹、森田 真規子、澤 明、疋田 貴俊、西 昭徳
    • Organizer
      第45回日本神経精神薬理学会
    • Place of Presentation
      タワーホール船堀(東京都・船堀)
    • Year and Date
      2015-09-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] Chronic fluoxetine treatment induces morphological changes of the perforant path synapse in the dentate gyrus: analysis of synaptic fine structures with FIB-SEM2015

    • Author(s)
      Kitahara Y, Ohta K, Shuto T, Kuroiwa M, Sotogaku N, Hasuo H, Togo A, Nakamura K, Nishi A
    • Organizer
      The 11th Chinese Neuroscience Society
    • Place of Presentation
      Wuzhen (China)
    • Year and Date
      2015-09-20
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] DISC1マウスの隔離飼育に対するcAMP/PKAシグナル応答:ホスホジエステラーゼの役割2015

    • Author(s)
      黒岩 真帆美、首藤 隆秀、外角 直樹、森田 真規子、澤 明、疋田 貴俊、西 昭徳
    • Organizer
      第38回日本神経科学大会
    • Place of Presentation
      神戸国際会議場(兵庫県・神戸市)
    • Year and Date
      2015-07-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] 抗うつ薬の慢性投与は海馬歯状回ドーパミンD1受容体シグナルを増強する2015

    • Author(s)
      黒岩 真帆美、首藤 隆秀、外角 直樹、西 昭徳
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋国際会議場(愛知・名古屋)
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Research-status Report
  • [Presentation] ドーパミンD1受容体アゴニスト併用投与によるSSRIのマウスうつ様行動に対する治療効果の増強2015

    • Author(s)
      首藤 隆秀、黒岩 真帆美、外角 直樹、西 昭徳
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋国際会議場(愛知・名古屋)
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Research-status Report
  • [Presentation] ドーパミンD1受容体アゴニストとSSRIの併用投与がマウスのうつ様行動に与える影響2014

    • Author(s)
      27.首藤隆秀、黒岩真帆美、外角直樹、西 昭徳
    • Organizer
      第67回日本薬理学会西南部会
    • Place of Presentation
      産業医科大学(福岡・北九州)
    • Year and Date
      2014-11-23
    • Related Report
      2014 Research-status Report
  • [Presentation] Altered regulation of cAMP/PKA signaling by PDE10A and PDE4 in DISC1 mutant mice.2014

    • Author(s)
      24.Nishi A, Kuroiwa M, Shuto T, Sotogaku N, Morita M, Sawa A, Hikida T
    • Organizer
      Annual Meeting of Society for Neuroscience (SfN)
    • Place of Presentation
      ワシントンDC(アメリカ)
    • Year and Date
      2014-11-15 – 2014-11-19
    • Related Report
      2014 Research-status Report
  • [Presentation] Social isolated DISC1 mutant mice displayed high sensitivity to chronic cocaine exposure and rolipram treatment.2014

    • Author(s)
      25.Hikida T, Morita M, Niwa M, Kuroiwa M, Hanna Jaaro-Peled, Sawa A, Nishi A
    • Organizer
      Annual Meeting of Society for Neuroscience (SfN)
    • Place of Presentation
      ワシントンDC(アメリカ)
    • Year and Date
      2014-11-15 – 2014-11-19
    • Related Report
      2014 Research-status Report
  • [Presentation] Chronic fluoxetine induces the enlargement of perforant path synapse in the dentate gyrus: 3D ultrastructural analyses using FIB/SEM.2014

    • Author(s)
      26.Kitahara Y, Ohta K, Shuto T, Kuroiwa M, Sotogaku N, Hasuo H, Togo A, Nakamura K, Nishi A.
    • Organizer
      Annual Meeting of Society for Neuroscience (SfN)
    • Place of Presentation
      ワシントンDC(アメリカ)
    • Year and Date
      2014-11-15 – 2014-11-19
    • Related Report
      2014 Research-status Report
  • [Presentation] Effect of chronic fluoxetine on the morphology of perforant path synapse in the dentate gyrus: 3D ultrastructural analyses using FIB/SEM.2014

    • Author(s)
      19.北原陽介、太田啓介、首藤隆秀、黒岩真帆美、外角直樹、蓮尾 博、都合亜記暢、中村桂一郎、西 昭徳
    • Organizer
      第37回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜(神奈川・横浜)
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Research-status Report
  • [Presentation] Role of PDE-mediated signaling and its crosstalk in brain function.2014

    • Author(s)
      Nishi A, Kuroiwa M, Shuto S, Snyder GL
    • Organizer
      CINP2014
    • Place of Presentation
      バンクーバー(カナダ)
    • Year and Date
      2014-06-22 – 2014-06-26
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2025-11-19  

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