• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Cognitive dysfunction in animal model of schizophrenia induced by neonatal glutamate receptor blockade and recovery by antipsychotics

Research Project

Project/Area Number 19K03365
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 10040:Experimental psychology-related
Research InstitutionUniversity of Tsukuba

Principal Investigator

ICHITANI Yukio  筑波大学, 人間系(名誉教授), 名誉教授 (80176289)

Co-Investigator(Kenkyū-buntansha) 山田 一夫  筑波大学, 人間系, 教授 (30282312)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsグルタミン酸受容体 / 統合失調症 / 認知機能障害 / 抗精神病薬 / ラット
Outline of Research at the Start

統合失調症は陽性・陰性症状、認知症状を呈する精神疾患であるが、このうち認知機能障害については発症メカニズムの解明、薬物療法の開発が遅れている。統合失調症の動物モデルとして、本研究では新生仔期にグルタミン酸NメチルDアスパラギン酸(NMDA)受容体を慢性遮断したラットを用いる。この動物の認知機能障害に及ぼす効果を調べるため、非定型の抗精神病薬投与による空間的記憶機能、注意機能の改善効果をテストする。さらに、新生仔期NMDA受容体遮断とその後の長期社会的隔離(孤立飼育)を組み合わせたモデルを導入して、新奇物体再認機能を加えてテストし、認知機能障害の特徴と薬物による改善の可能性を検索する。

Outline of Final Research Achievements

Animal model of schizophrenia was produced by neonatal chronic treatment of glutamatergic N-methyl-D-aspartate (NMDA)receptor antagonist in rats. Effects of atypical antipsychotics on cognitive dysfunction shown in these animals at adult stage were investigated. 1)Radial maze learning was severely disturbed and the impairment could be reduced by administration of aripiprazole. 2) Latent inhibition phenomenon (CS pre-exposure effect) was not disturbed. 3) Two-hit approach of neonatal NMDA receptor blockade combined with long-term isolation rearing after weaning showed that the combination of two treatments did not produce severer effects on novel object recognition test and radial maze performance compared with the single interventions.

Academic Significance and Societal Importance of the Research Achievements

統合失調症は複数の症状を呈する精神疾患であるが、認知機能障害については発症メカニズムの解明や薬物療法の開発が遅れている。本研究は、新生仔期のグルタミン酸受容体慢性遮断による記憶障害が臨床的に人の統合失調症治療で用いられている薬物で改善されるのかを調べ、この動物モデルの妥当性を検討した。また、離乳後の孤立飼育を組み合わせるtwo-hitモデルを導入して、新生仔期の受容体遮断に加えその後の社会的隔離というストレス状態を第2の衝撃として負荷した際に、認知機能障害が出現するのかを検討した。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (28 results)

All 2021 2020 2019 Other

All Journal Article (7 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 7 results,  Open Access: 3 results) Presentation (16 results) (of which Int'l Joint Research: 2 results) Remarks (5 results)

  • [Journal Article] Long-term associative memory in rats: Effects of familiarization period in object-place-context recognition test2021

    • Author(s)
      Shimoda Shota、Ozawa Takaaki、Ichitani Yukio、Yamada Kazuo
    • Journal Title

      PLoS ONE

      Volume: 16 Issue: 7 Pages: e0254570-e0254570

    • DOI

      10.1371/journal.pone.0254570

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pharmacologically induced N‐methyl‐D‐aspartate receptor hypofunction impairs goal‐directed food seeking in rats2021

    • Author(s)
      Ozawa Takaaki、Itokazu Tatsumi、Ichitani Yukio、Yamada Kazuo
    • Journal Title

      Neuropsychopharmacology Reports

      Volume: 41 Issue: 4 Pages: 526-531

    • DOI

      10.1002/npr2.12209

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prior stress experience modulates social preference for stressed conspecifics in male rats2021

    • Author(s)
      Toyoshima Michimasa、Mitsui Koshiro、Yamada Kazuo
    • Journal Title

      Neuroscience Letters

      Volume: 765 Pages: 136253-136253

    • DOI

      10.1016/j.neulet.2021.136253

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CRISPR/Cas9-engineered Gad1 elimination in rats leads to complex behavioral changes: implications for schizophrenia2020

    • Author(s)
      Fujihara Kazuyuki、Yamada Kazuo、Ichitani Yukio、Kakizaki Toshikazu、Jiang Weiru、Miyata Shigeo、Suto Takashi、Kato Daiki、Saito Shigeru、Watanabe Masahiko、Kajita Yuki、Ohshiro Tomokazu、Mushiake Hajime、Miyasaka Yoshiki、Mashimo Tomoji、Yasuda Hiroki、Yanagawa Yuchio
    • Journal Title

      Translational Psychiatry

      Volume: 10 Issue: 1 Pages: 426-426

    • DOI

      10.1038/s41398-020-01108-6

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enhanced methamphetamine-induced conditioned place preference in risk-taking rats2020

    • Author(s)
      Takahashi Katsumasa、Toyoshima Michimasa、Ichitani Yukio、Yamada Kazuo
    • Journal Title

      Behavioural Brain Research

      Volume: 378 Pages: 112299-112299

    • DOI

      10.1016/j.bbr.2019.112299

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Differential effects of N-methyl-D-aspartate receptor blockade during the second and third postnatal weeks on spatial working and reference memory in adult rats2019

    • Author(s)
      Furuie Hiroki、Yamada Kazuo、Ichitani Yukio
    • Journal Title

      Brain Research

      Volume: 1721 Pages: 146339-146339

    • DOI

      10.1016/j.brainres.2019.146339

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] D-Cycloserine reverses scopolamine-induced object and place memory deficits in a spontaneous recognition paradigm in rats2019

    • Author(s)
      Ozawa Takaaki、Yamada Kazuo、Ichitani Yukio
    • Journal Title

      Pharmacology Biochemistry and Behavior

      Volume: 187 Pages: 172798-172798

    • DOI

      10.1016/j.pbb.2019.172798

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Pharmacologically-induced N-methyl-D-aspartate receptor hypofunction impairs goal-directed food seeking in rats2021

    • Author(s)
      Ozawa, T., Itokazu, T., Ichitani, Y. & Yamada, K.
    • Organizer
      日本動物心理学会第81回大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Rats can remember a specific "roommate": a novel behavioral test using sensory preconditioning to assess individual recognition in rats2021

    • Author(s)
      Toyoshima, M. & Yamada., K.
    • Organizer
      日本動物心理学会第81回大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] The relationship between risk-taking behaviors and methamphetamine-induced conditioned place preference in rats2021

    • Author(s)
      Takahashi, K., Ichitani, Y. & Yamada, K.
    • Organizer
      50th Annual Meeting of the Society for Neuroscience
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Direct and indirect prior stress exposure modulates preference for stressed conspecifics in male rats2021

    • Author(s)
      Toyoshima, M., Okuda, E. & Yamada, K.
    • Organizer
      Society for Behavioral Neuroendocrinology, 25th Annual Meeting
    • Related Report
      2021 Annual Research Report
  • [Presentation] Role of the retrosplenial cortex in the retrieval of spatial context memory2021

    • Author(s)
      Shimoda, S., Ozawa, T. & Yamada, K.
    • Organizer
      第44回日本神経科学大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ラットの時間的順序記憶における内側前頭前野グルタミン酸受容体の役割2020

    • Author(s)
      椙田麻菜美・山田一夫・一谷幸男
    • Organizer
      第38回日本生理心理学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 恐怖条件づけの消去におけるアデノシン受容体阻害薬の影響2020

    • Author(s)
      加瀬田晃大・小澤貴明・一谷幸男・山田一夫
    • Organizer
      第43回日本神経科学大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 社会的再認記憶における海馬下位領域の関与:高記憶負荷条件における社会的記憶の脳内機構の検討2019

    • Author(s)
      豊島理公・山田一夫・椙田麻菜美・一谷幸男
    • Organizer
      第37回日本生理心理学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] ラットのストレスレジリエンスの個体差における扁桃体基底外側核内ニューロペプチドY投与の効果2019

    • Author(s)
      上野将玄・山田一夫・一谷幸男
    • Organizer
      第37回日本生理心理学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] ラットにおけるストレスレジリエンスと不安様行動・強迫様行動の関連:週齢と個体差からの検討2019

    • Author(s)
      上野将玄・山田一夫・一谷幸男
    • Organizer
      日本心理学会第83回大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 学習の速さと記憶促進薬の効果には個体差がある:空間記憶の記銘におけるラットの個体差とD-cycloserineの効果2019

    • Author(s)
      下田翔太・五十嵐優香・小澤貴明・山田一夫・一谷幸男
    • Organizer
      日本心理学会第83回大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Caffeine facilitates fear extinction in rats2019

    • Author(s)
      加瀬田晃大・小澤貴明・一谷幸男・山田一夫
    • Organizer
      日本動物心理学会第79回大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Socially enriched housing modifies pro-social behaviors in male rats2019

    • Author(s)
      豊島理公・森元紗雪・一谷幸男・山田一夫
    • Organizer
      日本動物心理学会第79回大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Effects of neonatal maternal separation on risk-taking behaviors in male and female rats2019

    • Author(s)
      高橋克匡・一谷幸男・山田一夫
    • Organizer
      日本動物心理学会第79回大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Prior stress experience modulates social preference for stressed conspecifics in male rats2019

    • Author(s)
      三井鴻志郎・豊島理公・一谷幸男・山田一夫
    • Organizer
      日本動物心理学会第79回大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Effects of serotonergic lesion of the dorsal raphe nucleus and the median raphe nucleus on fear extinction in rats2019

    • Author(s)
      Nakazawa, S., Ozawa, T., Ichitani, Y. & Yamada, K.
    • Organizer
      49th Annual Meeting of the Society for Neuroscience
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Remarks] 筑波大学人間系 教員情報

    • URL

      http://www.human.tsukuba.ac.jp/faculty_j/ichitani-yukio

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
  • [Remarks] 筑波大学大学院人間総合科学学術院 ニューロサイエンス学位プログラム 行動神経科学グループ 山田研究室

    • URL

      http://www.kansei.tsukuba.ac.jp/~ichitanilab/

    • Related Report
      2021 Annual Research Report
  • [Remarks] 筑波大学大学院人間総合科学学術院 ニューロサイエンス学位プログラム 行動神経科学グループ

    • URL

      http://www.kansei.tsukuba.ac.jp/~ichitanilab/

    • Related Report
      2020 Research-status Report
  • [Remarks] 筑波大学大学院 人間総合科学研究科 行動神経科学分野 一谷・山田グループ

    • URL

      http://www.kansei.tsukuba.ac.jp/~ichitanilab/

    • Related Report
      2019 Research-status Report
  • [Remarks] 筑波大学人間系心理学域 研究領域とスタッフ

    • URL

      http://www.human.tsukuba.ac.jp/psyche/institute/p02.php

    • Related Report
      2019 Research-status Report

URL: 

Published: 2019-04-18   Modified: 2023-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi