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2011 Fiscal Year Final Research Report

Elucidation of mechanisms regulating impulsivity in the developmental disorders and its pharmacotherapy : From a viewpoint of brain reward system

Research Project

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Project/Area Number 21790515
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Applied pharmacology
Research InstitutionNagasaki International University (2010-2011)
Hokkaido University (2009)

Principal Investigator

YAMAGUCHI Taku  長崎国際大学, 薬学部, 准教授 (80325563)

Project Period (FY) 2009 – 2011
Keywords発達障害 / 注意欠如多動性障害 / 衝動性 / SHRSP/Ezo / SHR亜系 / 行動解析 / 網羅的一塩基遺伝子多型解析 / 幼若期ストレス / 薬物治療
Research Abstract

In this study, to elucidate the mechanisms regulating impulsivity in the developmental disorders, I mainly explored the key neuronal molecules related to the expression/formation of impulsive behaviors in model rats of developmental disorder. I investigated using the juvenile stroke-prone spontaneous hypertensive rat (SHRSP/Ezo: Ezo) as an appropriate animal model of "attention deficit hyperactivity disorder (ADHD)" and we also used juvenile SHRSP/Izm (Izm) and SHRSP/Ngsk (Ngsk) which are similar to genetic background of Ezo in the SHR substrain. In comparison with juvenile WKY/Ezo which is a genetic control for Ezo, impulsive behavior in the elevated plus-maze test only observed in the Ezo, but not Izm and Ngsk, which behavioral properties were specific for Ezo. Base on the behavioral result, I explored the polymorphic regions linked Ezo-specific behavior differ from that of Izm and Ngsk using the database determined by global analysis of single nucleotide polymorphism (SNP). 137 SNPs linked Ezo-specific behavior were identified in the 21,032 candidate genes based on SNPs of Brown Norway rat. These SNPs linked Ezo-specific behavior were retained on the chromosome 7, 9 and X-chromosome. These findings suggested that genetic background associated with impulsive behavior in the Ezo as an ADHD model rat was related to the SNPs on the chromosome 7, 9 and X-chromosome and functional molecules linked to the development and formation of neuronal cells.

  • Research Products

    (42 results)

All 2012 2011 2010 2009 Other

All Journal Article (20 results) (of which Peer Reviewed: 18 results) Presentation (13 results) Book (7 results) Remarks (2 results)

  • [Journal Article] Lithium, but not valproic acid or carbamazepine, suppresses impulsivelike action in rats2012

    • Author(s)
      Ohmura Y., Tsutsui-Kimura I., Kumamoto H., Minami M., Izumi T., Yamaguchi T., Yoshida T, Yoshioka M.
    • Journal Title

      Psychopharmacology (Berl)

      Volume: 219 Pages: 421-432

    • DOI

      DOI:10.1007/s00213-011-2496-9

    • Peer Reviewed
  • [Journal Article] 幼若期ストレスによる成長後の情動行動障害2012

    • Author(s)
      山口拓、富樫廣子、松本真知子、泉剛、吉岡充弘
    • Journal Title

      日本薬理学雑誌

      Volume: 139 Pages: 142-146

    • URL

      https://www.jstage.jst.go.jp/article/fpj/139/4/139_4_142/_pdf

  • [Journal Article] Juvenile stress attenuates the dorsal hippocampal postsynaptic 5-HT1A receptor function in adult rats2011

    • Author(s)
      Matsuzaki H, Izumi T, Horinouchi T, Boku S, Inoue T, Yamaguchi T, Yoshida T, Matsumoto M, Togashi H, Miwa S, Koyama T, Yoshioka M
    • Journal Title

      Psychopharmacology (Berl)

      Volume: 214 Pages: 329-337

    • DOI

      DOI:10.1007/s00213-010-1987-4

    • Peer Reviewed
  • [Journal Article] Serotonin1A receptormadiated synaptic responses in the rat medial prefrontal cortex is altered by early life stress: In vivo and in vitro electrophysiological studies2011

    • Author(s)
      Kimura S, Togashi H, Matsumoto M, Shiozawa T, Ishida J, Kano S, Ohashi A, Ishikawa S, Yamaguchi T, Yoshioka M, Shimamura K.
    • Journal Title

      Jpn J Neuropsychopharmacol

      Volume: 31 Pages: 9-15

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/21404951

    • Peer Reviewed
  • [Journal Article] Retrieval of conditioned fear activates the basolateral and intercalated nucleus of amygdala2011

    • Author(s)
      Izumi T, Boku S, Shinmin W, Inoue T, Konno K, Yamaguchi T, Yoshida T, Matsumoto M, Watanabe M, Koyama T, Yoshioka M.
    • Journal Title

      J Neurosci Res.

      Volume: 89 Pages: 773-790

    • DOI

      DOI:10.1002/jnr.22592

    • Peer Reviewed
  • [Journal Article] Inhibition of noradrenaline release by clonidine in the ventral bed nucleus of the stria terminalis attenuates pain-induced aversion in rats2011

    • Author(s)
      Deyama S, Ide S, Kondoh N, Yamaguchi T, Yoshioka M, Minami M.
    • Journal Title

      Neuropharmacology

      Volume: 61 Pages: 156-160

    • DOI

      DOI:10.1016/j.neuropharm.2011.03.023

    • Peer Reviewed
  • [Journal Article] Regulation of cerebral blood flow in the hippocampus by neuronal activation through the perforant path: Relationship between hippocampal blood flow and neuronal plasticity2011

    • Author(s)
      Hamadate N., Yamaguchi T., Sugawara A., Tsujimatsu A., Izumi T, Yoshida T, Ohmura Y, Yoshioka M.
    • Journal Title

      Brain Res.

      Volume: 1415 Pages: 1-7

    • DOI

      DOI:10.1016/j.brainres.2011.08.008

    • Peer Reviewed
  • [Journal Article] The serotonergic projection from the median raphe nucleus to the ventral hippocampus is involved in the retrieval of fear memory via the corticotropinreleasing factor type 2 receptor2010

    • Author(s)
      Ohmura Y, Izumi T, Yamaguchi T, Tsutsui-Kimura I, Yoshida T, Yoshioka M
    • Journal Title

      Neuropsychopharmacology

      Volume: 35 Pages: 1271-1278

    • DOI

      DOI:10.1038/npp.2009.229

    • Peer Reviewed
  • [Journal Article] Nicotine provokes impulsive-like action by stimulating alpha4beta2 nicotinic acetylcholine receptors in the infralimbic, but not in the prelimbic cortex2010

    • Author(s)
      Tsutsui-Kimura I, Ohmura Y, Izumi T, Yamaguchi T, Yoshida T, Yoshioka M
    • Journal Title

      Psychopharmacology

      Volume: 209 Pages: 351-359

    • DOI

      DOI:10.1007/s00213-010-1804-0

    • Peer Reviewed
  • [Journal Article] Endogenous acetylcholine modulates impulsive action via α4β2 nicotinic acetylcholine receptors in rats2010

    • Author(s)
      Tsutsui-Kimura I, Ohmura Y, Izumi T, Yamaguchi T, Yoshida T, Yoshioka M
    • Journal Title

      Eur J Pharmacol

      Volume: 641 Pages: 148-153

    • DOI

      DOI:10.1007/s00213-010-1804-0

    • Peer Reviewed
  • [Journal Article] Therapeutic potentials of an artificial oxygen-carrier, liposomeencapsulated hemoglobin, for ischemia/reperfusion-induced cerebral dysfunction in rats2010

    • Author(s)
      Kakehata J, Yamaguchi T, Togashi H, Sakuma I, Otani H, Morimoto Y, Yoshioka M
    • Journal Title

      J. Pharmacol Sci.

      Volume: 114 Pages: 189-197

    • DOI

      DOI:10.1254/jphs.10115FP

    • Peer Reviewed
  • [Journal Article] Diazepam-induced increases of synaptic efficacy in the hippocampal-medial prefrontal cortex pathway are associated with its anxiolytic-like effect of rats2010

    • Author(s)
      Shikanai H., Izumi T., Matsumoto M., Togashi H., Yamaguchi T., Yoshida T., Yoshioka M.
    • Journal Title

      J. Pharmacol Sci.

      Volume: 114 Pages: 341-346

    • DOI

      DOI:10.1254/jphs.10182FP

    • Peer Reviewed
  • [Journal Article] Liposome-encapsulated hemoglobin ameliorates impairment of fear memory and hippocampal dysfunction after cerebral ischemia in rats2010

    • Author(s)
      Hamadate N., Yamaguchi T., Sugawara A., Togashi H., Izumi T, Yoshida T, Ohmura Y, Yoshioka M.
    • Journal Title

      J. Pharmacol Sci.

      Volume: 114 Pages: 409-419

    • DOI

      DOI:10.1254/jphs.10207FP

    • Peer Reviewed
  • [Journal Article] Effect of parabolic flight on plasma arginine vasopressin as a sensitive marker for psycho-physiological stress in human2010

    • Author(s)
      Yoshioka M., Yamaguchi T., Gyotoku J., Ochiai T., Ohta H.
    • Journal Title

      Biol Sci Space

      Volume: 24 Pages: 95-100

    • URL

      http://dx.doi.org/10.2187/bss.24.95

    • Peer Reviewed
  • [Journal Article] Role of enhanced β-adrenergic transmission within the ventral bed nucleus of the stria terminalis in visceral pain-induced aversion in rats2009

    • Author(s)
      Deyama S, Katayama T, Kondoh N, Nakagawa T, Kaneko S, Yamaguchi T., Yoshioka M, Minami M
    • Journal Title

      Behav Brain Res

      Volume: 197 Pages: 279-283

    • DOI

      DOI:10.1016/j.bbr.2008.08.024

    • Peer Reviewed
  • [Journal Article] Corticotropin releasing factor enhances attentional function as assessed by the five-choice serial reaction time task in rats2009

    • Author(s)
      Ohmura Y, Yamaguchi T., Futami Y, Togashi H, Izumi T, Matsumoto M, Yoshida T, Yoshioka M.
    • Journal Title

      Behav Brain Res

      Volume: 198 Pages: 429-433

    • DOI

      DOI:10.1016/j.bbr.2008.11.025

    • Peer Reviewed
  • [Journal Article] Possible relationship between the stress-induced synaptic response and metaplaticity in the hippocampal CA1 field of freely moving rats2009

    • Author(s)
      Hirata R, Matsumoto M, Judo C, Yamaguchi T, Izumi T, Yoshioka M, Togashi H
    • Journal Title

      Synapse

      Volume: 63 Pages: 549-556

    • DOI

      DOI:10.1002/syn.20631

    • Peer Reviewed
  • [Journal Article] Early postnatal stress affects 5-HT1A receptor function in the medial prefrontal cortex in adult rats., Eur J Pharmacol2009

    • Author(s)
      Matsuzaki H, Izumi T, Matsumoto M, Togashi H, Yamaguchi T, Yoshida T, Watanabe M, Yoshioka M
    • Journal Title

      Eur J Pharmacol

      Volume: 615 Pages: 76-82

    • DOI

      DOI:10.1002/syn.20631

    • Peer Reviewed
  • [Journal Article] The effects of serotonin and/or noradrenaline reuptake inhibitors on impulsive-like action assessed by the three-choice serial reaction time task: a simple and valid model of impulsive action using rats2009

    • Author(s)
      Tsutsui-Kimura I, Ohmura Y, Izumi T, Yamaguchi T, Yoshida T, Yoshioka M
    • Journal Title

      Behav Pharmacol

      Volume: 20 Pages: 474-843

    • DOI

      DOI:10.1097/FBP.0b013e3283305e65

    • Peer Reviewed
  • [Journal Article] 既存薬から新しい薬効を探し出す

    • Author(s)
      山口拓
    • Journal Title

      ファルマシア

      Volume: 46 Pages: 463-464

    • URL

      http://jglobal.jst.go.jp/public/20090422/201002257333689360

  • [Presentation] SHR亜系統における注意欠如多動性障害モデルラットとしてのSHRSP/Ezoの特異性2011

    • Author(s)
      山口拓、富樫廣子、小嶋希望、芹川忠夫、吉岡充弘
    • Organizer
      第21回日本臨床精神神経薬理学会・第41回日本神経精神薬理学会合同年会
    • Place of Presentation
      東京
    • Year and Date
      20111027-29
  • [Presentation] Liposome-encapsulated hemoglobin ameliorates brain dysfunction after cerebral ischemia in rats2011

    • Author(s)
      Yamaguchi T., Hamadate N., Sugawara A., Togashi H., Yamamoto T., Yoshioka M.
    • Organizer
      2nd Congress of Asian College of Neuropsychopharmacology
    • Place of Presentation
      Seoul
    • Year and Date
      20110923-24
  • [Presentation] SHR亜系と行動特性 : 中枢神経系からみたSHR亜系と表現型の多様性2011

    • Author(s)
      山口拓、富樫廣子、芹川忠夫、吉岡充弘
    • Organizer
      第47回高血圧関連疾患モデル学会学術総会
    • Place of Presentation
      札幌(招待講演)
    • Year and Date
      20110906-07
  • [Presentation] 幼若期ストレスによる社会的行動障害 : 多様なライフステージにおける精神疾患発症に関わる環境因子とその創薬標的としての可能性2011

    • Author(s)
      山口拓
    • Organizer
      第84回日本薬理学年会
    • Place of Presentation
      横浜(招待講演)
    • Year and Date
      20110322-24
  • [Presentation] SHR亜系統における注意欠如多動性障害モデルラットとしてのSHRSP/Ezoの行動特異性とその関連遺伝子座位の探索2011

    • Author(s)
      山口拓、富樫廣子、芹川忠夫、吉岡充弘
    • Organizer
      第64回日本薬理学会西南部会
    • Place of Presentation
      福岡
    • Year and Date
      2011-11-20
  • [Presentation] Social deficits and GABAergic dysfunction of the raphe nuclei in adolescent and postadolescent rats experienced with early postnatal stress2010

    • Author(s)
      Yamaguchi T., Sugio H., Konno K., Matsuzaki H., Izumi T., Yoshioka M.
    • Organizer
      Society for neuroscience 40th annual meeting
    • Place of Presentation
      San Diego
    • Year and Date
      20101113-17
  • [Presentation] 一過性脳虚血モデルラットの異常行動と人工酸素運搬体の改善効果2010

    • Author(s)
      山口拓、濱舘直史、掛端 仁、富樫廣子、泉剛、吉田隆行、吉岡充弘
    • Organizer
      第38回薬物活性シンポジウム
    • Place of Presentation
      札幌(招待講演)
    • Year and Date
      20101111-12
  • [Presentation] 行動薬理学概論・各論(1)一般行動の評価法2010

    • Author(s)
      山口拓
    • Organizer
      新薬理学セミナー2010(トライアル) : ~はじめての行動薬理学~
    • Place of Presentation
      札幌(招待講演)
    • Year and Date
      2010-09-09
  • [Presentation] 行動薬理学各論(2)抑うつ・不安関連行動の評価法2010

    • Author(s)
      山口拓
    • Organizer
      新薬理学セミナー2010(トライアル) : ~はじめての行動薬理学~
    • Place of Presentation
      札幌(招待講演)
    • Year and Date
      2010-09-09
  • [Presentation] セロトニン5-HT_<1A>受容体を介した抑肝散の抗不安効果2010

    • Author(s)
      山口拓、辻松亜記、泉剛、吉田隆行、吉岡充弘
    • Organizer
      第14回活性アミンに関するワ-クショップ
    • Place of Presentation
      仙台
    • Year and Date
      2010-08-27
  • [Presentation] 注意欠如・多動性障害モデルラットにおける多動性、注意機能障害および衝動的行動に対する選択的ノルアドレナリン再取り込み阻害薬atomoxetineの改善効果2009

    • Author(s)
      山口拓、富樫廣子、鈴木直哉、小嶋希望、松本真知子、泉剛、吉田隆行、吉岡充弘
    • Organizer
      第19回日本臨床精神神経薬理学会・第39回日本神経精神薬理学会合同年会
    • Place of Presentation
      京都
    • Year and Date
      20091113-15
  • [Presentation] Atypical antipsychotics ameliorate the impulsive behavior via serotonin 5-HT_<2A> receptors in an ADHD model rat2009

    • Author(s)
      Yamaguchi T., Togashi H., Izumi T., Yoshida T., Yoshioka M.
    • Organizer
      Society for neuroscience 39th annual meeting
    • Place of Presentation
      Chicago
    • Year and Date
      20091017-21
  • [Presentation] 注意欠如・多動性障害モデルラット、幼若SHRSP/Ezo~衝動性における行動薬理学的特性 : 病因・病態仮説に基づく精神疾患モデルの開発と創薬への応用2009

    • Author(s)
      山口拓、富樫廣子、松本真知子、泉剛、吉田隆行、吉岡充弘
    • Organizer
      第82回日本薬理学年会
    • Place of Presentation
      横浜(招待講演)
    • Year and Date
      20090316-18
  • [Book] 第8章「不安・恐怖」、心理学研究法3-学習・動機・情動(廣中直行編)2011

    • Author(s)
      山口拓、富樫廣子、吉岡充弘
    • Total Pages
      185-203
    • Publisher
      誠信書房
  • [Book] 第1編 基礎編 : 行動薬理研究における実験技術「6.不安関連行動の評価法」、実験薬理学「実践行動薬理学」(日本薬理学会編)2010

    • Author(s)
      山口拓、吉岡充弘
    • Total Pages
      43-52
    • Publisher
      金芳堂
  • [Book] 第2編 応用編 : 行動薬理研究の実際 第1章 情動機構関連「4.情動ストレスと臨界期脳機能発達-幼若期ストレスによる情動行動障害-」、実験薬理学「実践行動薬理学」(日本薬理学会編)2010

    • Author(s)
      山口拓、富樫廣子、松本真知子、泉剛、吉田隆行、吉岡充弘
    • Total Pages
      147-157
    • Publisher
      金芳堂
  • [Book] 急性ストレス反応 : 基礎実験、ストレス百科事典-Encyclopedia of Stress 2^<nd> ed.、日本ストレス学会2009

    • Author(s)
      山口拓、吉岡充弘
    • Publisher
      丸善
  • [Book] 拘束ストレス、ストレス百科事典-Encyclopedia of Stress 2^<nd> ed.、日本ストレス学会2009

    • Author(s)
      山口拓、吉岡充弘
    • Publisher
      丸善
  • [Book] アデニル酸シクラーゼ、ストレス百科事典-Encyclopedia of Stress 2^<nd> ed.、日本ストレス学会2009

    • Author(s)
      山口拓、吉岡充弘
    • Publisher
      丸善
  • [Book] ストレス低反応期、ストレス百科事典-Encyclopedia of Stress 2^<nd> ed.、日本ストレス学会2009

    • Author(s)
      山口拓、吉岡充弘
    • Publisher
      丸善
  • [Remarks]

    • URL

      http://hokudaineuropharmacol.com/

  • [Remarks]

    • URL

      http://www1.niu.ac.jp/about/teacher/detail.html?data[id]=250

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Published: 2013-07-31  

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