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Effect of administration of morphine on the synthesis of D-serine in rat brain

Research Project

Project/Area Number 19603016
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pain science
Research InstitutionTokai University

Principal Investigator

YOSHIKAWA Masanobu  Tokai University, 医学部, 講師 (90276791)

Co-Investigator(Kenkyū-buntansha) 橋本 篤司  東海大学, 医学部, 准教授 (80271592)
Co-Investigator(Renkei-kenkyūsha) HASHIMOTO Atushi  東海大学, 医学部, 准教授 (80271592)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords疼痛学 / Dセリン / セリンラセマーゼ / モルヒネ / 鎮痛 / 耐性 / NMDA受容体 / 鎮痛作用 / 下行性痛覚抑制経路 / ミダゾラム / ベンゾジアゼピン / in situ hybridization / 神経細胞
Research Abstract

モルヒネ慢性投与によりラット脳内においてDセリン合成酵素のセリンラセマーゼ(Srr) mRNA量およびタンパク質量が増加すること、前脳部(大脳皮質、線状体、海馬)においてDセリン量が増加すること、Srrが神経細胞で主に発現していることを明らかにした。これらの結果より、モルヒネの鎮痛耐性が形成される際にN-メチル-アスパラギン酸(NMDA)受容体が活性化される機序として、Dセリン量の増加が関与する可能性が示唆された。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (31 results)

All 2009 2008 2007

All Journal Article (19 results) (of which Peer Reviewed: 19 results) Presentation (12 results)

  • [Journal Article] The antinociceptive effects of midazolam on three different types of nociception in mice2009

    • Author(s)
      Chiba S, Nishiyama T, Yoshikawa M, Yamada Y
    • Journal Title

      J Pharmacol Sci 109(1)

      Pages: 71-77

    • NAID

      10025733715

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibitory effect of low-dose pentazocine on the development of antinociceptive tolerance to morphine2009

    • Author(s)
      Chiba S, Hayashida M, Yoshikawa M, Shu H, Nishiyama T, Yamada Y
    • Journal Title

      J Anesthesia 23(1)

      Pages: 99-107

    • NAID

      10025381744

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] The serine racemase mRNA is expressed in both neurons and glial cells of rat retina2008

    • Author(s)
      Takayasu N, Yoshikawa M, Watanabe M, Tsukamoto H, Suzuki T, Kobayashi H, Noda S
    • Journal Title

      Arch Histol Cytol 71(2)

      Pages: 123-129

    • NAID

      10025095752

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Long-term treatment with morphine increases the D-serine content in the rat brain by regulating the mRNA and protein expressions of serine racemase and D-amino acid oxidase2008

    • Author(s)
      Yoshikawa M, Shinomiya T, Takayasu N, Tsukamoto H, Kawaguchi M, Kobayashi H, Oka T, Hashimoto A
    • Journal Title

      J Pharmacol Sci 107(3)

      Pages: 270-276

    • NAID

      10024321297

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mice lacking D-amino acid oxidase activity exhibit marked reduction of methamphetamine -induced stereotypy2008

    • Author(s)
      Hashimoto A, Konno R, Yano H, Yoshikawa M, Tamaki R, Matsumoto H, Kobayashi H
    • Journal Title

      Eur J Pharmacol 856(1-3)

      Pages: 221-225

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Midazolam attenuates the antinociception induced by D-serine or morphine at the supraspinal level in rats2008

    • Author(s)
      Ito K, Yoshikawa M, Maeda M, Jin XL, Takahashi S, Matsuda M, Tamaki R, Kobayashi H, Suzuki T, Hashimoto A
    • Journal Title

      Eur J Pharmacol 856(1-3)

      Pages: 139-144

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Acute administration of methamphetamine decreases the mRNA expression of diazepam binding expression of diazepam bindinginhibitor in rat brain2008

    • Author(s)
      Tamaki R, Yoshikawa M, Shinomiya T, Hashimoto A, Kawaguchi M, Bryne WD, Kobayashi H
    • Journal Title

      Tokai J Exp Clin Tokai J Exp Clin Med 33(1)

      Pages: 51-56

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chronic administration of methamphetamine increases the mRNA expression of diazepam binding inhibitor in rat brain2008

    • Author(s)
      Tamaki R, Yoshikawa M, Shinomiya T, Andoh H, Kawaguchi M, Hashimoto A, Bryne WD, Kobayashi H
    • Journal Title

      Tokai J Exp Clin Med 33(1)

      Pages: 46-50

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Great increase in antinociceptive potency of [Leu5]enkephalin after peptidase inhibition2008

    • Author(s)
      Akahori K, Kosaka K, Jin XL, Arai Y, Yoshikawa M, Kobayashi H, Oka T
    • Journal Title

      J Pharmacol Sci 106(2)

      Pages: 295-300

    • NAID

      10024318545

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Long-Term Treatment With Morphine Increases the D-Seine Content in the Rat Brain by Regulating the mRNA and Protein Expressions of Serine Racemase and D-Amino Acid Oxidase2008

    • Author(s)
      Masanobu Yoshikawa
    • Journal Title

      Journal of Pharmacological Sciences 107

      Pages: 270-276

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Midazolam attenuates the antinociception induced by D-serine or morphine at the supraspinal level in rats2008

    • Author(s)
      Kenji Ito
    • Journal Title

      European Journal of Pharmacology 586

      Pages: 139-144

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The serine racemase mRNA is expressed in both neurons and glial cells of the rat retina2008

    • Author(s)
      Naoko Takayasu
    • Journal Title

      Archives of Histology and Cytoglogy 71

      Pages: 123-129

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Midazolam attenuates the antinociception induced by D-serine or morphine at the supraspinal level in rats2008

    • Author(s)
      Kenji Ito, et. al.
    • Journal Title

      European Journal of Pharmacology (In Press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The enhancing effects of peptidase inhibitors on antinociceptive action of [Met5]enkephalin-Arg6-Phe7 in rats2007

    • Author(s)
      Takahashi S, Jin XL, Kosaka K, Yoshikawa M, Kobayashi H, Oka T
    • Journal Title

      J Pharmacol Sci 105(1)

      Pages: 117-121

    • NAID

      10024315987

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] The serine racemase mRNA is predominantly expressed in rat brain neurons2007

    • Author(s)
      Yoshikawa M, Takayasu N, Hashimoto A, Sato Y, Tamaki R, Tsukamoto H, Kobayashi H, Noda S
    • Journal Title

      Arch Histol Cytol 70(2)

      Pages: 127-134

    • NAID

      10019551068

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Activation of supraspinal NMDA receptors by both D-serine alone or in combination with morphine leads to the potentiation of antinociception in tail-flick test of rats2007

    • Author(s)
      Yoshikawa M, Ito K, Maeda M, Akahori K, Takahashi S, Jin XL, Matsuda M, Suzuki T, Oka T, Kobayashi H, Hashimoto A
    • Journal Title

      Eur J Pharmacol 565(1-3)

      Pages: 89-97

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of MK-801 on the expression of serine racemase and D-amino acid oxidase mRNAs and on the D-serine levels in rat brain2007

    • Author(s)
      Hashimoto A, Yoshikawa M, Andoh H, Yano H, Matsumoto H, Kawaguchi M, Oka T, Kobayashi H
    • Journal Title

      Eur J Pharmacol 555(1)

      Pages: 17-22

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] The serine racemase mRNA is predominantly expressed in rat brain neurons2007

    • Author(s)
      Masanobu Yoshikawa, et. al.
    • Journal Title

      Archives of Histology and Cytology 70

      Pages: 127-134

    • NAID

      10019551068

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of supraspinal NMDA receptor by both D-serine alone or in combination with morphine leads to the potentiation of antinociception in tail flick test of rats2007

    • Author(s)
      Masanobu Yoshikawa, et. al.
    • Journal Title

      European Journal of Pharmacology 565

      Pages: 89-97

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] セリンラセマーゼ遺伝子のラット眼組織における発現について2009

    • Author(s)
      野田節子, 高安直子, 渡辺真理子, 吉川正信
    • Organizer
      第114回日本解剖学会総会・全国学術集会
    • Year and Date
      2009-03-28
    • Related Report
      2008 Final Research Report
  • [Presentation] ケタミン長期投与によるDセリン代謝関連酵素遺伝子発現の変化2009

    • Author(s)
      渡邊真理子, 吉川正信, 竹山和秀, 村田智彦, 金幸禄, 小林智美, 橋本篤司, 小林広幸, 鈴木利保
    • Organizer
      第82回日本薬理学会年会
    • Year and Date
      2009-03-16
    • Related Report
      2008 Final Research Report
  • [Presentation] Long-term treatment with morphine increases the D-serine content in the rat brain by regulating the mRNA and protein expressions of serine racemase and D-amino acid oxidase2008

    • Author(s)
      Masanobu Yoshikawa
    • Organizer
      Neuroscience 2008
    • Place of Presentation
      Washington DC
    • Year and Date
      2008-11-20
    • Related Report
      2008 Annual Research Report
  • [Presentation] Long-term treatment with morphine increases the D-serine content in the rat brain by regulating the mRNA and protein expressions of serine racemase and D-amino acid oxidase2008

    • Author(s)
      M.Yoshikawa, A.Hashimoto, H.Kobayashi
    • Organizer
      Neuroscience 2008
    • Year and Date
      2008-11-17
    • Related Report
      2008 Final Research Report
  • [Presentation] ラット脳室内および髄腔内投与によるL-702,324の鎮痛効果に対する作用2008

    • Author(s)
      前田美保, 松田光正, 鈴木利保, 吉川正信, 橋本篤司
    • Organizer
      日本ペインクリニック学会第42回大会
    • Year and Date
      2008-07-18
    • Related Report
      2008 Final Research Report
  • [Presentation] ホルマリンテストでのD-serineの鎮痛効果2008

    • Author(s)
      松田光正, 吉川正信, 前田美保, 伊藤健二, 鈴木利保
    • Organizer
      日本麻酔科学会第55回学術集会
    • Year and Date
      2008-06-14
    • Related Report
      2008 Final Research Report
  • [Presentation] メタンフェタミン投与によるジアゼパムバインディングインヒビター遺伝子発現の変化2008

    • Author(s)
      玉記雷太, 吉川正信, 四宮敬史, 橋本篤司, 川口充, 小林広幸
    • Organizer
      第118回日本薬理学会関東部会
    • Year and Date
      2008-06-07
    • Related Report
      2008 Final Research Report
  • [Presentation] セリンラセマーゼ遺伝子のラット脳神経細胞における発現について2008

    • Author(s)
      野田節子, 高安直子, 佐藤 雄一, 橋本篤司, 小林広幸, 吉川正信
    • Organizer
      第113回日本解剖学会総会・全国学術集会
    • Year and Date
      2008-03-27
    • Related Report
      2008 Final Research Report
  • [Presentation] セリンラセマーゼ遺伝子のラット脳神経細胞における発現について2008

    • Author(s)
      野田 節子, 他
    • Organizer
      第113回日本解剖学会総会・全国学術集会
    • Place of Presentation
      大分大学医学部
    • Year and Date
      2008-03-27
    • Related Report
      2007 Annual Research Report
  • [Presentation]2008

    • Author(s)
      吉川正信, 四宮敬史, 小林智美, 赤堀一仁, 橋本篤司, 小林広幸, 川口充
    • Organizer
      第81回日本薬理学会年会
    • Year and Date
      2008-03-17
    • Related Report
      2008 Final Research Report
  • [Presentation] セリンラセマーゼmRNAは主に神経細胞において発現する2007

    • Author(s)
      吉川 正信, 他
    • Organizer
      第50回神経化学会大会
    • Place of Presentation
      パシヒコ横浜
    • Year and Date
      2007-09-11
    • Related Report
      2007 Annual Research Report
  • [Presentation] セリンラセマーゼmRNAは主に神経細胞において発現する2007

    • Author(s)
      吉川正信, 高安直子, 野田節子, 佐藤雄一, 小林広幸, 橋本篤司
    • Organizer
      第50回神経化学会大会
    • Year and Date
      2007-09-10
    • Related Report
      2008 Final Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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