Study for molecular and neural mechanisms underlying abused druginduced neuropsychosis using organotypic slice cultures

2009 Fiscal Year Final Research Report

• Project/Area Number: 20790062
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: Kyoto University
• Principal Investigator: NAKAGAWA Takayuki Kyoto University, 薬学研究科, 准教授 (30303845)
• Project Period (FY): 2008 – 2009
• Keywords: 薬理学 / 精神疾患 / メタンフェタミン / MDMA / 依存性薬物 / 脳切片培養系 / 中脳皮質辺縁ドパミン神経 / 縫線核セロトニン神経

Research Abstract

We found that repeated exposure to various types of abused drugs, such as methamphetamine, cocaine and morphine, commonly induced the augmentation of dopamine release (dopaminergic sensitization) in the rat mesocorticolimbic dopaminergic slice co-cultures. Furthermore, in rat raphe serotonergic slice culture, sustained exposure to MDMA induced marked augmentation of exocytotic serotonin release, which is different from acute MDMA-evoked serotonin efflux.

Research Products

• [Journal Article] 脳内グリア細胞におけるtransient receptor potential channelの病態生理的役割. (2010)
  • Author(s): 白川久志、中川貴之、金子周司
  • Journal Title: 薬学雑誌 130 Pages: 281-287
• [Journal Article] Role of enhanced noradrenergic transmission within the ventral bed nucleus of the stria terminalis in visceral pain-induced aversion in rats. (2009)
  • Author(s): Deyama S, Katayama T, Kondoh N, Nakagawa T, Kaneko S, Yamaguchi T, Yoshioka M, Minami M
  • Journal Title: Behav Brain Res 197 Pages: 279-283
• [Journal Article] オピオイド受容体の多様性と役割分担. (2009)
  • Author(s): 中川貴之、佐藤公道
  • Journal Title: 生体の科学 60 Pages: 446-447
• [Journal Article] ノシセプチンとその受容体. (2009)
  • Author(s): 中川貴之、佐藤公道
  • Journal Title: 生体の科学 60 Pages: 486-487
• [Journal Article] Augmentation of serotonin release by sustained exposure to 3, 4-methylenedioxymethamphetamine and methamphetamine in rat organotypic mesencephalic slice cultures containing raphe serotonergic neurons. (2008)
  • Author(s): Higuchi M, Suzuki Y, Yatani Y, Kitagawa Y, Nagayasu K, Shirakawa H, Nakagawa T, Kaneko S
  • Journal Title: J Neurochem 106 Pages: 2410-2420
• [Journal Article] Gene transfer of GLT-1, a glial glutamate transporter, into the spinal cord by recombinant adenovirus attenuates inflammatory and neuropathic pain in rats. (2008)
  • Author(s): Maeda S, Kawamoto A, Yatani Y, Shirakawa H, Nakagawa T, Kaneko S
  • Journal Title: Mol Pain 4 Pages: 65
• [Journal Article] Mechanisms of substrate transport-induced clustering of a glial glutamate transporter GLT-1 in astroglial-neuronal cultures. (2008)
  • Author(s): Nakagawa T, Otsubo Y, Yatani Y, Shirakawa H, Kaneko S
  • Journal Title: Eur J Neurosci 28 Pages: 1719-1730
• [Journal Article] Ractive oxygen species derived from NOX1/NADPH oxidase enhance inflammatory pain. (2008)
  • Author(s): Ibi M, Matsuno K, Shiba D, Katsuyama M, Iwara K, Kakehi T, Nakagawa T, Sango K, Shirai Y, Yokoyama T, Kaneko S, Saito N, Yabe-Nishimura C
  • Journal Title: J Neurosci 28 Pages: 9486-9494
• [Journal Article] Differential contribution of spinal mitogen-activated protein kinases to the phase of long-lasting allodynia evoked by intrathecal administration of ATP in rats. (2008)
  • Author(s): Nakagawa T, Wakamatsu K, Maeda S, Shirakawa H, Kaneko S
  • Journal Title: Biol Pharm Bull 31 Pages: 1164-1168
• [Journal Article] Ca2+ mobilization mediated by transient receptor potential canonical 3 is associated with thrombin-induced morphological changes of 1321N1 human astrocytoma cells. (2008)
  • Author(s): Nakao K, Shirakawa H, Sugishita A, Matsutani I, Niidome T, Nakagawa T, Kaneko S
  • Journal Title: J Neurosci Res 86 Pages: 2722-2732
• [Journal Article] TRPV1 stimulation triggers apoptotic cell death of rat cortical neurons. (2008)
  • Author(s): Shirakawa H, Yamaoka T, Sanpei K, Sasaoka, H, Nakagawa T, Kaneko S
  • Journal Title: Biochem Biophys Res Commun 377 Pages: 1211-1215
• [Journal Article] Activation of the β-adrenoceptor-protein kinase A signaling pathway within the ventral bed nucleus of the stria terminalis mediates the negative affective component of pain in rats. (2008)
  • Author(s): Deyama S, Katayama T, Nakagawa T, Kaneko S, Yamaguchi T, Yoshioka M, Minami M
  • Journal Title: J Neurosci 28 Pages: 7728-7736
• [Journal Article] Dibutyryl cyclic AMP induces differentiation of human neuroblastoma SH-SY5Y cells into a noradrenergic phenotype. (2008)
  • Author(s): Kume T, Kawato Y, Osakada F, Izumi Y, Katsuki H, Nakagawa T, Kaneko S, Niidome T, Takada-Takatori Y, Akaike A
  • Journal Title: Neurosci Lett 443 Pages: 199-203
• [Journal Article] 薬物依存症とモノアミントランスポーター. (2008)
  • Author(s): 中川貴之
  • Journal Title: Clin Neurosci 26 Pages: 1140-1142
• [Journal Article] グルタミン酸トランスポーターと中枢神経系疾患. (2008)
  • Author(s): 中川貴之
  • Journal Title: 医学のあゆみ 225 Pages: 1348-1349
• [Journal Article] 脳切片培養系を用いた依存性薬物の精神神経毒性評価-薬物依存のin vitro研究- (2008)
  • Author(s): 中川貴之、金子周司
  • Journal Title: 日本アルコール・薬物医学会雑誌 43 Pages: 166-171
• [Journal Article] Neuropsychotoxicity of abused drugs: Molecular and neural mechanisms of neuropsychotoxicity induced by methamphetamine, 3, 4-methylenedioxy methamphetamine (Ecstasy) and 5-methoxy- N, N-diisopropyltryptamine (Foxy). (2008)
  • Author(s): Nakagawa T, Kaneko S
  • Journal Title: J Pharmacol Sci 106 Pages: 2-8
• [Journal Article] Sustained exposure to 3, 4-methylenedioxymethamphetamine induces the augmentation of exocytotic serotonin release in rat organotypic raphe slice cultures.
  • Author(s): Nagayasu K, Kitaichi M, Shirakawa H, Nakagawa T, Kaneko S
  • Journal Title: J Pharmacol Sci (in press)
• [Journal Article] 神経-グリア回路網の機能異常を原因とする慢性疼痛及び薬物依存に関する研究.
  • Author(s): 中川貴之
  • Journal Title: 日本薬理学雑誌 (in press)
• [Presentation] 縫線核セロトニン神経含有中脳冠状切片におけるSSRI持続処置によるセロトニン遊離増強現象のメカニズム (2010)
  • Author(s): 中川貴之、永安一樹、八谷有美、北市麻衣子、白川久志、金子周司
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 20100328-20100330
• [Presentation] 第25回日本薬理学会学術奨励賞受賞講演「神経-グリア回路網の機能異常を原因とする慢性疼痛及び薬物依存に関する研究」 (2010)
  • Author(s): 中川貴之
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪
  • Year and Date: 20100316-20100318
• [Presentation] Molecular basis of sustained MDMA induced augmentation of 5-HT release in raphe serotonergic slice culture (2009)
  • Author(s): Nagayasu, K., Higuchi, M., Kitaichi, M., Shirakawa, H., Nakagawa, T., Kaneko, S.
  • Organizer: 第39回日本神経精神薬理学会年会
  • Place of Presentation: 京都国際会館
  • Year and Date: 20091113-20091115
• [Presentation] Molecular biological analyses of the augmentation of 5-HT release by sustained MDMA in organotypic raphe slice culture(縫線核含有中脳切片培養系における依存性薬物MDMA慢性処置によるセロトニン遊離増強現象の分子生物学的解析) (2009)
  • Author(s): 永安一樹、中川貴之、樋口萌、八谷有美、白川久志、金子周司
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋
  • Year and Date: 20090916-20090918
• [Presentation] Mechanisms of serotonergic sensitization induced by sustained MDMA exposure in rat organotypic mesencephalic slice cultures (2009)
  • Author(s): Nakagawa T, Higuchi M, Nagayasu K, Suzuki Y, Yatani Y, Shirakawa H, Kaneko S
  • Organizer: IUPS2009 (XXXVI th International Union of Physiological Sciences)
  • Place of Presentation: Kyoto
  • Year and Date: 20090727-20090801
• [Presentation] TRPM2チャネルの精神機能および慢性疼痛における役割:TRPM2ノックアウトマウスを用いた行動解析 (2009)
  • Author(s): 中川貴之、白川久志、前田早苗、山口健太郎、河本愛、草野綾香、森泰生、金子周司
  • Organizer: 第5回TRPチャネル研究会
  • Place of Presentation: 岡崎生理研
  • Year and Date: 20090604-20090605
• [Presentation] 縫線核セロトニン神経含有中脳切片培養系におけるセロトニントランスポーター阻害薬(SSRI)および基質型遊離薬(MDMA)長期処置による影響 (2009)
  • Author(s): 中川貴之、永安一樹、樋口萌、八谷有美、北川寛、白川久志、金子周司
  • Organizer: 第4回トランスポーター研究会
  • Place of Presentation: 東大
  • Year and Date: 20090523-20090524
• [Presentation] セロトニン神経含有脳切片に対する依存性薬物MDMAの長期的作用 (2009)
  • Author(s): 永安一樹、樋口萌、八谷有美、白川久志、中川貴之、金子周司
  • Organizer: 次世代を担う創薬・医療薬理シンポジウム2009
  • Place of Presentation: 慶応義塾大
  • Year and Date: 2009-08-24
• [Presentation] セロトニントランスポーターを介した基質輸送および放出の分子メカニズムの解析 (2009)
  • Author(s): 上西良泳、白川久志、中川貴之、金子周司
  • Organizer: 第115回日本薬理学会近畿部会
  • Place of Presentation: 金沢
  • Year and Date: 2009-06-26
• [Presentation] シンポジウム『精神神経疾患とトランスポーター』「脳切片培養系を用いた精神神経疾患とモノアミントランスポーター研究」 (2009)
  • Author(s): 中川貴之
  • Organizer: 第18回神経行動薬理若手研究者の集い
  • Place of Presentation: 横浜
  • Year and Date: 2009-03-19
• [Presentation] 縫線核含有中脳切片培養系における選択的セロトニン再取り込み阻害薬持続的処置によるセロトニン遊離の増強作用 (2008)
  • Author(s): 八谷有美、北川寛、樋口萌、永安一樹、更田宏史、白川久志、中川貴之、金子周司
  • Organizer: 第2回次世代を担う若手医療薬科学シンポジウム
  • Place of Presentation: 京都大・薬
  • Year and Date: 20081220-20081221
• [Presentation] 縫線核含有中脳切片培養系における選択的セロトニン再取り込み阻害薬持続的処置によるセロトニン遊離の増強作用 (2008)
  • Author(s): 中川貴之、八谷有美、樋口萌、北川寛、白川久志、金子周司
  • Organizer: 第38回日本神経精神薬理学会・第18回日本臨床精神神経薬理学会合同年会
  • Place of Presentation: 品川
  • Year and Date: 20081001-20081003
• [Presentation] グリア型グルタミン酸トランスポーターGLT-1のエンドサイトーシスの分子機構 (2008)
  • Author(s): 中川貴之、大坪泰斗、八谷有美、白川久志、金子周司
  • Organizer: 生体機能と創薬シンポジウム2008東京
  • Place of Presentation: 星薬科大学
  • Year and Date: 20080905-20080906
• [Presentation] Mechanisms of serotonergic sensitization induced by sustained MDMA treatment in rat organotypic mesencephalic slice culture (2008)
  • Author(s): 中川貴之、樋口萌、鈴木祐一、白川久志、金子周司
  • Organizer: Neuroscience2008(第31回日本神経科学大会)
  • Place of Presentation: 東京
  • Year and Date: 20080709-20080711
• [Presentation] 縫線核含有中脳冠状切片培養系における選択的セロトニン再取り込み阻害薬持続的処置によるセロトニン遊離の増強作用 (2008)
  • Author(s): 八谷有美、北川寛、樋口萌、白川久志、中川貴之、金子周司
  • Organizer: 第3回トランスポーター研究会年会
  • Place of Presentation: 京都
  • Year and Date: 20080607-20080608
• [Remarks]
  • URL: http://www.pharm.kyoto-u.ac.jp/seikai/nakagawa.html