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Research on serotonergic neurons projecting to the prefrontal cortex as a target of drug development against psychiatric disorders

Research Project

Project/Area Number 22590249
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionNippon Medical School

Principal Investigator

SUZUKI Hidenori  日本医科大学, 大学院・医学研究科, 教授 (30221328)

Co-Investigator(Kenkyū-buntansha) SAITOW Fumihito  日本医科大学, 医学部, 准教授 (20360175)
NAGANO Masatoshi  日本医科大学, 医学部, 講師 (60271350)
KOBAYASHI Katsunori  日本医科大学, 医学部, 講師 (10322041)
SAKAI Atsushi  日本医科大学, 医学部, 助教 (30386156)
SATO Hiromasa  日本医科大学, 医学部, 助教 (50386744)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords5-HT 受容体 / 中脳背側縫線核 / セロトニン神経細胞 / GABA 作動性神経細胞 / 不安障害 / 選択的セロトニン再取り込み阻害薬 / 前頭前野 / 海馬 / ストレス / 不安様行動 / 5-HT2A/2C受容体 / 5-HT1A受容体 / GABA作動性神経細胞 / GAD67-GFPマウス / セロトニン神経系 / 5-HT1_Aセロトニン受容体作働薬 / 脳由来神経栄養因子 / D_1ドパミン受容体 / 5-HT_4セロトニン受容体 / 5-HT_<1A>セロトニン受容体
Research Abstract

In rats with late-emerging anxiety symptoms, decreased expression of 5-HT_1A receptor (5-HT_1A-R) mRNA was observed in the medial prefrontal cortex (mPFC) before emerging of the abnormal behaviors. Early therapeutic interventions with serotonergic drugs prevented the anxiety symptoms in the rats in association with normalization of5-HT1A-R mRNA expression. In the dorsal raphe nucleus innervating mPFC, electrophysiology revealed that various current responses were elicited by serotonin in GABAergic cells viamultiple 5-HT receptor subtypes, including 5-HT_1A, 5-HT_2A/2C and 5-HT_7.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (30 results)

All 2013 2012 2011 2010 Other

All Journal Article (11 results) (of which Peer Reviewed: 11 results) Presentation (14 results) (of which Invited: 1 results) Book (2 results) Remarks (3 results)

  • [Journal Article] Electrophysiological and pharmacological properties of GABAergic cells in the dorsal raphe nucleu2013

    • Author(s)
      Gocho Y
    • Journal Title

      Journal of Physiological Sciences

      Volume: 63 Issue: 2 Pages: 147-154

    • DOI

      10.1007/s12576-012-0250-7

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chronic fluoxetine selectively upregulates dopamine D1-like receptors in the hippocampus.2012

    • Author(s)
      Kobayashi K, Haneda E, Higuchi M, SuharaT, Suzuki H.
    • Journal Title

      Neuropsychopharmacology

      Volume: 37 Issue: 6 Pages: 1500-1508

    • DOI

      10.1038/npp.2011.335

    • Related Report
      2012 Annual Research Report 2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Early intervention with fluoxetine reverses abnormalities in the serotonergic system and behavior of rats exposed prenatally to dexamethasone2012

    • Author(s)
      Masatoshi Nagano, Mingyan Liu, Hirofumi Inagaki, Tomoyuki Kawada
    • Journal Title

      Hidenori Suzuki Neuropharmacology

      Volume: (in press) Issue: 2 Pages: 292-300

    • DOI

      10.1016/j.neuropharm.2012.03.027

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Functional magnetic resonance imaging study on the effects of acute single administration of paroxetine on motivation-related brain activity2011

    • Author(s)
      Marutani, T., Yahata, N., Ikeda, Y., Ito, T., Yamamoto, M., Matsuura, M., Okubo, Y., Matsushima, E., Suzuki, H. & Matsuda, T.
    • Journal Title

      Psychiatry Clin Neurosci

      Volume: 65 Issue: 2 Pages: 191-198

    • DOI

      10.1111/j.1440-1819.2011.02189.x

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Behavioral destabilization induced by the selective serotonin reuptake inhibitor fluoxetine2011

    • Author(s)
      Kobayashi K, Ikeda Y, Suzuki H.
    • Journal Title

      Mol Brain

      Volume: 4 Issue: 1 Pages: 12-12

    • DOI

      10.1186/1756-6606-4-12

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Modulatory effects of serotonin on glutamatergic synaptic transmission and long-term depression in the deep cerebellar nuclei2011

    • Author(s)
      Murano M, Saitow F, Suzuki H
    • Journal Title

      Neurosci

      Volume: 172 Pages: 118-128

    • DOI

      10.1016/j.neuroscience.2010.10.037

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Modulatory effects of serotonin on glutamatergic synaptic transmission and long-term depression in the deep cerebellar nuclei.2011

    • Author(s)
      Murano M
    • Journal Title

      Neuroscience

      Volume: 172 Pages: 118-128

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Behavioral destabilization induced by the selective serotonin reuptake inhibitor fluoxetine.2011

    • Author(s)
      Kobayashi K
    • Journal Title

      Mol Brain

      Volume: 4 Pages: 12-12

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reversal of hippocampal neuronal maturation by serotonergic antidepressants2010

    • Author(s)
      Kobayashi K, Ikeda Y, Sakai A, Yamasaki N, Haneda E, Miyakawa T, Suzuki H.
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 107 Issue: 18 Pages: 8434-9

    • DOI

      10.1073/pnas.0912690107

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Reversal of hippocampal neuronal maturation by serotonergic antidepressants.2010

    • Author(s)
      Kobayashi K
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 107 Pages: 8434-8439

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Early intervention with fluoxetine reverses abnormalities in the serotonergic system and behavior of rats exposed prenatally to dexamethasone

    • Author(s)
      Nagano M
    • Journal Title

      Neuropharmacol

      Volume: (In press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] マウス背側縫線核におけるニューロンの電気生理学的特性2013

    • Author(s)
      牛腸義宏,齋藤文仁,柳川右千夫,坂井敦,鈴木秀典
    • Organizer
      第90回日本生理学会大会
    • Place of Presentation
      タワーホール船堀(東京)
    • Related Report
      2012 Final Research Report
  • [Presentation] マウス背側縫線核におけるニューロンの電気生理学的特性2013

    • Author(s)
      牛腸義宏
    • Organizer
      第90回日本生理学会大会
    • Place of Presentation
      タワーホール船堀(東京)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 胎児期ストレス誘導性の行動異常とセロトニンシグナリング2012

    • Author(s)
      永野昌俊
    • Organizer
      第18回「性と生殖」公開シンポジウム第5回早稲田大学-日本医科大学合同シンポジウム
    • Place of Presentation
      早稲田大学国際会議場(東京)
    • Year and Date
      2012-12-22
    • Related Report
      2012 Final Research Report
  • [Presentation] 小脳核苔状線維におけるモノアミン作動性受容体のクロストーク2012

    • Author(s)
      齋藤文仁,鈴木秀典
    • Organizer
      活性アミンに関するワークショップ
    • Place of Presentation
      北海道医療大学札幌サテライトキャンパス(北海道)
    • Year and Date
      2012-08-24
    • Related Report
      2012 Final Research Report
  • [Presentation] フルオキセチンによる早期介入が胎生期にグルココルチコイドに暴露されたラットにおけるセロトニン神経系と行動の異常を改善する2012

    • Author(s)
      永野昌俊,劉明妍,鈴木秀典
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋国際会議場(愛知)
    • Related Report
      2012 Final Research Report
  • [Presentation] 縫線核におけるGABA作動性ニューロンの形態的特徴と電気生理学的特性の解析2012

    • Author(s)
      牛腸義宏,齋藤文仁,柳川右千夫,鈴木秀典
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋国際会議場(愛知)
    • Related Report
      2012 Final Research Report
  • [Presentation] フルオキセチンによる早期介入が胎生期にグルココルチコイドに暴露されたラットにおけるセロトニン神経系と行動の異常を改善する2012

    • Author(s)
      永野昌俊
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋国際会議場
    • Related Report
      2012 Annual Research Report
  • [Presentation] 縫線核におけるGABA作動性ニューロンの形態的特徴と電気生理学的特性の解析2012

    • Author(s)
      牛腸義宏
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋国際会議場
    • Related Report
      2012 Annual Research Report
  • [Presentation] セロトニン5-HT4受容体欠損マウスにおける恐怖条件付けのメス特異的な亢進2011

    • Author(s)
      小林克典
    • Organizer
      第34回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2011-09-17
    • Related Report
      2011 Annual Research Report
  • [Presentation] セロトニン5-HT4受容体欠損マウスにおける恐怖条件付けのメス特異的な亢進2011

    • Author(s)
      小林克典、三ケ原靖規、長濱健一郎、鈴木秀典
    • Organizer
      日本神経科学大会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Related Report
      2012 Final Research Report
  • [Presentation] Effects of early intervention with fluoxetine on anxiety-related behaviors induced in prenatally glucocorticoid exposed rats.2010

    • Author(s)
      Nagano M
    • Organizer
      16th World Congress of Basic and Clinical Pharmacology (WorldPharma 2010)
    • Place of Presentation
      Copenhagen, Denmark
    • Year and Date
      2010-07-20
    • Related Report
      2010 Annual Research Report
  • [Presentation] Effects of early intervention with fluoxetine on anxiety-related behaviors induced in prenatally glucocorticoid exposed rats2010

    • Author(s)
      Nagano M, Liu M, Ozawa H, Suzuki H
    • Organizer
      16th World Congress of Basic and Clinical Pharmacology (WorldPharma 2010)
    • Place of Presentation
      Copenhagen (Denmark)
    • Related Report
      2012 Final Research Report
  • [Presentation] 胎児期ストレス誘導性の行動異常とセロトニンシグナリング

    • Author(s)
      永野昌俊
    • Organizer
      第18回「性と生殖」公開シンポジウム 第5回早稲田大学-日本医科大学合同シンポジウム
    • Place of Presentation
      早稲田大学・国際会議場
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 小脳核苔状線維におけるモノアミン作動性受容体のクロストーク

    • Author(s)
      齋藤文仁
    • Organizer
      活性アミンに関するワークショップ
    • Place of Presentation
      北海道医療大学 札幌サテライトキャンパス
    • Related Report
      2012 Annual Research Report
  • [Book] Serotonin and Synaptic Transmission in the Cerebellum In: Handbook of the Cerebellum and Cerebellar Disorders, (eds. M. Manto, D.L. Gruol, J.D. Schmahmann, N.Koibuchi, F. Rossi)2012

    • Author(s)
      Saitow F, Hirono M, Suzuki H
    • Publisher
      Springer
    • Related Report
      2012 Final Research Report
  • [Book] Handbook of the Cerebellum and Cerebellar Disorders2012

    • Author(s)
      Saitow F
    • Total Pages
      12
    • Publisher
      Springer
    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.nms.ac.jp/nms/pharmacol/

    • Related Report
      2012 Final Research Report
  • [Remarks]

    • URL

      http://www.nms.ac.jp/nms/pharmacol/

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.nms.ac.jp/nms/pharmacol/

    • Related Report
      2010 Annual Research Report

URL: 

Published: 2010-08-23   Modified: 2019-07-29  

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