The relationship between psychosis induced by ketamine and D-serine synthesis

2008 Fiscal Year Final Research Report

• Project/Area Number: 19591820
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Tokai University
• Principal Investigator: TAKEYAMA Kazuhide Tokai University, 医学部, 講師 (80256148)
• Co-Investigator(Kenkyū-buntansha): YOSHIKAWA Masanobu 東海大学, 医学部, 講師 (90276791)
• Co-Investigator(Renkei-kenkyūsha): HASHIMOTO Atushi 東海大学, 医学部, 准教授 (80271592)
• Project Period (FY): 2007 – 2008
• Keywords: 疼痛管理学

Research Abstract

Wistar系雄性ラットにケタミンを長期投与(50mg/kg/day, 14days)した結果、ラット前脳部(大脳皮質、海馬、線状体)および間脳のセリンラセマーゼ遺伝子発現が有意に増加し、中脳においてDアミノ酸酸化酵素遺伝子発現が有意に減少した。これらの結果は、N-メチル-アスパラギン酸(NMDA)受容体拮抗薬であるケタミン投与により、NMDA受容体の内在性リガンドのDセリンが代償として増加することが示唆された。

Research Products

• [Journal Article] The antinociceptive effects of midazolam on three different types of nociception in mice (2009)
  • Author(s): Chiba S, Nishiyama T, Yoshikawa M, Yamada Y
  • Journal Title: J Pharmacol Sci 109(1) Pages: 71-77
  • Peer Reviewed
• [Journal Article] Inhibitory effect of low-dose pentazocine on the development of antinociceptive tolerance to morphine (2009)
  • Author(s): Chiba S, Hayashida M, Yoshikawa M, Shu H, Nishiyama T, Yamada Y
  • Journal Title: J Anesthesia 23(1) Pages: 99-107
  • Peer Reviewed
• [Journal Article] The serine racemase mRNA is expressed in both neurons and glial cells of rat retina (2008)
  • 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
  • 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 oxidase (2008)
  • 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
  • Peer Reviewed
• [Journal Article] Mice lacking D-amino acid oxidase activity exhibit marked reduction of methamphetamine -induced stereotypy (2008)
  • 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
  • Peer Reviewed
• [Journal Article] Midazolam attenuates the antinociception induced by D-serine or morphine at the supraspinal level in rats (2008)
  • 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
  • Peer Reviewed
• [Journal Article] Acute administration of methamphetamine decreases the mRNA expression of diazepam binding inhibitor in rat brain (2008)
  • Author(s): Tamaki R, Yoshikawa M, Shinomiya T, Hashimoto A, Kawaguchi M, Bryne WD, Kobayashi H
  • Journal Title: Tokai J Exp Clin Med 33(1) Pages: 51-56
  • Peer Reviewed
• [Journal Article] Chronic administration of methamphetamine increases the mRNA expression of diazepam binding inhibitor in rat brain (2008)
  • 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
  • Peer Reviewed
• [Journal Article] Great increase in antinociceptive potency of [Leu5]enkephalin after peptidase inhibition (2008)
  • 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
  • Peer Reviewed
• [Journal Article] The enhancing effects of peptidase inhibitors on antinociceptive action of [Met5]enkephalin-Arg6-Phe7 in rats (2007)
  • Author(s): Takahashi S, Jin XL, Kosaka K, Yoshikawa M, Kobayashi H, Oka T
  • Journal Title: J Pharmacol Sci 105(1) Pages: 117-121
  • Peer Reviewed
• [Journal Article] The serine racemase mRNA is predominantly expressed in rat brain neurons (2007)
  • 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
  • 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 rats (2007)
  • 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
  • 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 brain (2007)
  • 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
  • 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
• [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
• [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 oxidase. (2008)
  • Author(s): M.Yoshikawa, A.Hashimoto, H.Kobayashi
  • Organizer: Neuroscience 2008
  • Year and Date: 2008-11-17
• [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
• [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
• [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
• [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
• [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
• [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