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Investigation of the mechanisms on the emotional behaviors in mice via delta opioid receptors in prelimbic prefrontal cortex

Research Project

Project/Area Number 26461730
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Psychiatric science
Research InstitutionNational Center of Neurology and Psychiatry

Principal Investigator

Akiyoshi Saitoh  国立研究開発法人国立精神・神経医療研究センター, 精神保健研究所 精神薬理研究部, 室長 (00366832)

Co-Investigator(Kenkyū-buntansha) 山田 美佐  国立研究開発法人国立精神・神経医療研究センター, 精神保健研究所 精神薬理研究部, 科研費研究員 (10384182)
関口 正幸  国立研究開発法人国立精神・神経医療研究センター, 神経研究所 疾病研究第四部, 室長 (80260339)
岡 淳一郎  東京理科大学, 薬学部薬学科, 教授 (40134613)
山田 光彦  国立研究開発法人国立精神・神経医療研究センター, 精神保健研究所 精神薬理研究部, 部長 (60240040)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords行動薬理 / 精神薬理 / 行動薬理学 / 精神薬理学 / オピオイドδ受容体 / 情動行動 / 不安様行動 / 内側前頭前野前辺縁皮質領域 / 抗不安様作用
Outline of Final Research Achievements

The local co-perfusion of a selective δ opioid receptor (DOR) agonist KNT-127 with a sodium channel activator veratrine in prelimbic medial prefrontal cortex (PL-PFC) diminished the veratrine-induced anxiety-like behaviors and extracellular glutamate levels. Interestingly, KNT-127 diminished a glutamate transporter inhibitor TFB-TBOA-induced anxiety-like behaviors without effect on TFB-TBOA-induced extracellular glutamate levels. These inhibitory effects of KNT-127 were antagonized by the co-perfusion of a DOR antagonist NTI. Based on these results, we suggested that KNT-127 in the PL-PFC reduced anxiety-like behaviors by suppressing the pre/post-synaptically glutamatergic transmission, bidirectionally. We proposed that a DOR agonist KNT-127 that inhibits glutamatergic transmission in the PL-PFC is a possible candidate for a novel anxiolytic.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (13 results)

All 2017 2016 2015

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Acknowledgement Compliant: 5 results) Presentation (7 results) Book (1 results)

  • [Journal Article] Effects of repeated treatment with the delta opioid receptor agonist KNT-127 on hyperemotionality in olfactory-bulbectomized rats.2017

    • Author(s)
      Gotoh L, Saitoh A, Yamada M, Fujii H, Nagase H, Yamada M.
    • Journal Title

      Behav Brain Res.

      Volume: 323 Pages: 11-14

    • DOI

      10.1016/j.bbr.2016.11.008

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] The infralimbic and prelimbic medial prefrontal cortices have differential functions in the expression of anxiety-like behaviors in mice.2016

    • Author(s)
      Suzuki S, Saitoh A, Ohashi M, Yamada M, Oka JI,
    • Journal Title

      Behav Brain Res.

      Volume: 304 Pages: 120-124

    • DOI

      10.1016/j.bbr.2016.01.044

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Riluzole in the prelimbic medial prefrontal cortex attenuates veratrine-induced anxiety-like behaviors in mice.2015

    • Author(s)
      Ohashi M, Saitoh A, Yamada M, Oka JI, Yamada M.
    • Journal Title

      Psychopharmacology

      Volume: 232 Issue: 2 Pages: 391-398

    • DOI

      10.1007/s00213-014-3676-1

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Induction of c-Fos immunoreactivity in the amygdala of mice expressing anxiety-like behavior after local perfusion of veratrine in the prelimbic medial prefrontal cortex.2015

    • Author(s)
      Yamada M, Saitoh A, Ohashi M, Satoshi Suzuki, Oka JI, Yamada M.
    • Journal Title

      J Neural Transm.

      Volume: 122 Issue: 8 Pages: 1203-1207

    • DOI

      10.1007/s00702-015-1373-9

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] The voltage-gated sodium channel activator veratrine induces anxiogenic-like behaviors in rats.2015

    • Author(s)
      Saitoh A, Makino M, Hashimoto T, Yamada M, Sugiyama A, Ohashi M, Tsukagoshi, M, Oka J, Yamada M.
    • Journal Title

      Behav Brain Res.

      Volume: 292 Pages: 316-322

    • DOI

      10.1016/j.bbr.2015.06.022

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 内側前頭前野前辺縁皮質でオピオイドδ受容体作動薬KNT-127はマウスのベラトリン誘発性不安様行動を減弱する.2017

    • Author(s)
      137.斎藤顕宜、鈴木聡史、大橋正誠、早田暁伸、山田美佐、岡淳一郎、長瀬博、山田光彦
    • 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 Annual Research Report
  • [Presentation] 不飽和脂肪酸バランスによる条件性恐怖記憶のコントロール2016

    • Author(s)
      関口正幸
    • Organizer
      第38回日本生物学的精神医学会・第59回日本神経化学会大会合同年会
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      2016-09-08
    • Related Report
      2016 Annual Research Report
  • [Presentation] 内側前頭前野前辺縁皮質領域のオピオイドδ受容体は扁桃体へ投射しているグルタミン酸神経伝達を抑制し不安様行動を改善する.2016

    • Author(s)
      121.斎藤顕宜、鈴木聡史、早田暁伸、大橋正誠、山田美佐、長瀬博、岡淳一郎、山田光彦
    • Organizer
      第46回日本神経精神薬理学会年会
    • Place of Presentation
      韓国ソウルCOEX
    • Year and Date
      2016-07-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] マウスの不安様行動における内側前頭前野の役割を脳内微小透析法で探る.2016

    • Author(s)
      119.斎藤顕宜、鈴木聡史、早田暁伸、赤木希衣、山田美佐,岡淳一郎、山田光彦
    • Organizer
      第55回日本生体医工学会大会
    • Place of Presentation
      富山国際会議場
    • Year and Date
      2016-04-26
    • Related Report
      2015 Research-status Report
  • [Presentation] グルタミン酸神経系に作用する新しい抗うつ薬・抗不安薬の開発.2016

    • Author(s)
      斎藤顕宜、山田光彦
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-03-09
    • Related Report
      2015 Research-status Report
  • [Presentation] マウス内側前頭前野前辺縁皮質領域のグルタミン酸神経を介した不安様行動発現に対するオピオイドδ受容体作動薬KNT-127の影響.2015

    • Author(s)
      斎藤顕宜,鈴木聡史,早田暁伸,山田美佐,岡淳一郎,山田光彦
    • Organizer
      第26回マイクロダイアリシス研究会
    • Place of Presentation
      お茶の水女子大学
    • Year and Date
      2015-12-19
    • Related Report
      2015 Research-status Report
  • [Presentation] オピオイドδ受容体はマウス内側前頭前野前辺縁皮質領域において神経活動依存的にグルタミン酸神経系を調節する.2015

    • Author(s)
      早田暁伸,斎藤顕宜,鈴木聡史,山田美佐,岡淳一郎,山田光彦
    • Organizer
      生体機能と創薬シンポジウム
    • Place of Presentation
      日本大学薬学部
    • Year and Date
      2015-08-27
    • Related Report
      2015 Research-status Report
  • [Book] GPCR研究の最前線2016

    • Author(s)
      斎藤顕宜、山田光彦
    • Total Pages
      633
    • Publisher
      医学のあゆみ
    • Related Report
      2015 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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