Study for interaction between D-serine synthesis and development of morphine tolerance

• Project/Area Number: 20591843
• 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: ITO Kenji Tokai University, 医学部, 講師 (10317779)
• Co-Investigator(Kenkyū-buntansha): YOSHIKAWA Masanobu 東海大学, 医学部, 准教授 (90276791)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 疼痛管理学 / モルヒネ / 麻薬 / ケタミン / Dセリン / セリンラセマーゼ / Dアミノ酸酸化酵素 / 鎮痛 / 耐性 / in situ hybridization / 免疫組織化学 / NMDA受容体

Research Abstract

Repeated administration of morphine for 30 days produced a significant augmentations of both the mRNA and protein expressions of serine racemase in all the brain regions, and caused a slight but significant elevation in the elevated D-seirne revel in the cortex, striatum and hippocampus. The antinociception induced by the intracerebroventricular (i.c.v.) administration of D-serine was attenuated by i.c.v. administration of midazolam. These results indicate the elevated D-serine level following the chronic morphine treatment could at least in part be involved in the activation of NMDA receptors via the glycine site.

Research Products

• [Journal Article] Subchronic administration of Ketamine decreases the mRNA expression of serine racemase in rat brain (2010)
  • Author(s): M.Watanabe, M.Yoshikawa, K.Takeyama, et al
  • Journal Title: Tokai Journal of Experimental and Clinical Medicine Volume: 35 Pages: 137-143
  • Peer Reviewed
• [Journal Article] The antinociceptive effects of midazolam on three different types of nociception in mice (2009)
  • Author(s): hiba S, Nishiyama T, Yoshikawa M, Yamada Y
  • Journal Title: J Pharmacol Sci 109(1) Pages: 71-77
  • NAID: 10025733715
  • 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
  • NAID: 10025381744
  • 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
  • NAID: 10025095752
  • 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
  • NAID: 10024321297
  • 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
  • NAID: 10024318545
  • Peer Reviewed
• [Journal Article] Long-Torm Treatmont With Morphino Increases tho D-Seine Content in the Rat Brain by Regulating the mRNA and Protein Expressions of Serine Racemase and D-Amino Acid Oxidase (2008)
  • Author(s): Masanobu Yoshikawa
  • Journal Title: Journal of Pharmacological Sciences 107 Pages: 270-276
  • Peer Reviewed
• [Journal Article] Midazolam attenuates the antinociception induced by D-serine or morphine at the supraspinal level in rats (2008)
  • Author(s): Konji Ito
  • Journal Title: European Journal of Pharmacology 586 Pages: 139-144
  • Peer Reviewed
• [Journal Article] The serine racemase mRNA is expressed in both neurons and glial cells of the rat retina (2008)
  • Author(s): Naoko Takayasu
  • Journal Title: Archives of Histology and Cytology 71 Pages: 123-129
  • 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): Masanobu Yoshikawa
  • Organizer: Neuroscience 2008
  • Place of Presentation: WASHINGT0N, D. C. Conference Center
  • Year and Date: 2008-11-20
• [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): 4.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): 5.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いて (2008)
  • Author(s): 6.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