A study to clarify the pathogenesis of mood disorders based on the neurochemical mechanism of emotional stress in the amygdala

• Project/Area Number: 19591333
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Hokkaido University
• Principal Investigator: INOUE Takeshi Hokkaido University, 北海道大学病院, 講師 (70250438)
• Co-Investigator(Kenkyū-buntansha): NAKAGAWA Shin 北海道大学, 大学院・医学研究科, 助教 (60360905)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2007: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 気分障害 / 恐怖条件付け / 神経科学 / ストレス / 扁桃体 / セロトニン / 選択的セロトニン再取り込み阻害剤(SSRI) / SSRI / 抗不安作用 / CREB / セロトニン受容体サブタイプ

Research Abstract

情動ストレスの動物モデルを用いて、抗不安・抗うつ薬である選択的セロトニン(5-HT)再取り込み阻害薬(SSRI)の作用機序解明を行った。SSRIの効果は5-HT^<1A>受容体のアゴニストとアンタゴニスト、新規抗うつ薬mirtazapineの併用により増強することを見いだした。情動ストレスからの回復過程(消去)にラット脳扁桃体の一部(基底核と呼ばれる)が重要な役割をはたしていることが示唆された。

Research Products

• [Journal Article] Glucocorticoids and lithium reciprocally regulate the proliferation of adult dentate gyrus-derived neural precursor cells through GSK-3β andβ-catenin/TCF pathway (2009)
  • Author(s): Boku S, Nakagawa S, Masuda T, Nishikawa H, Kato A, Kitaichi Y, Inoue T, Koyama T
  • Journal Title: Neuropsychopharmacology 34 Pages: 805-815
  • Peer Reviewed
• [Journal Article] Effects of acute citalopram on the expression of conditioned freezing in naive versus chronic citalopram-treated rats (2009)
  • Author(s): Hashimoto S, Inoue T, Muraki I, Koyama T
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry 33 Pages: 113-117
  • Peer Reviewed
• [Journal Article] Anxiolytic-like profile of mirtazapine in rat conditioned fear stress model : Functional significance of 5-hydroxytryptamine 1A receptor and alpha1-adrenergic receptor (2009)
  • Author(s): Kakui N, Yokoyama F, Yamauchi M, Kitamura K, Imanishi T, Inoue T, Koyama T
  • Journal Title: Pharmacol Biochem Behav 92 Pages: 393-8
  • Peer Reviewed
• [Journal Article] 不安障害における扁桃体セロトニンの役割(シンポジウム「脳科学による心身医学の解明」) (2009)
  • Author(s): 井上 猛、小山 司
  • Journal Title: 心身医学 49 Pages: 291-297
• [Journal Article] 難治性うつ病に対するドパミン作動薬の有用性 (2009)
  • Author(s): 井上 猛、北市雄士、小山 司
  • Journal Title: 臨床精神薬理 12 Pages: 831-838
• [Journal Article] Effects of acute citalopram on the expression of conditioned freezing in naive versus chronic citaloaram-treated rats (2009)
  • Author(s): Hashimoto S, Inoue T, Muraki I, Koyama T
  • Journal Title: Prog Neuropsychopharmacol Bio Psychiatry 33 Pages: 113-117
  • Peer Reviewed
• [Journal Article] Effect of co-administration of the selective 5-HT1A receptor antagonist WAY 100,635 and selective 5-HT1B/1D receptor antagonist GR 127,935 on anxiolytic effect of citalopram in conditioned fear stress in the rat (2008)
  • Author(s): Muraki I, Inoue T, Koyama T
  • Journal Title: Eur J Pharmacol 586 Pages: 171-178
  • Peer Reviewed
• [Journal Article] Effect of co-administration of a serotonin- noradrenaline reuptake inhibitor and a dopamine agonist on extracellular monoamine concentrations in rats (2008)
  • Author(s): Kitaichi Y, Inoue T, Izumi T, Nakagawa S, Tanaka T, Masui T, Koyama T
  • Journal Title: Eur J Pharmacol 584 Pages: 285-290
  • Peer Reviewed
• [Journal Article] Changes in amygdala neural activity that occur with the extinction of context- dependent conditioned fear stress (2008)
  • Author(s): Izumi T, Inoue T, Kato A, Kitaichi Y, Nakagawa S, Koyama T
  • Journal Title: Biochem. Behav 90 Pages: 297-304
  • Peer Reviewed
• [Journal Article] Depressive patients are more impulsive and inconsistent in intertemporal choice behavior for monetary gain and loss than healthy subjects--an analysis based on Tsallis' statistics (2008)
  • Author(s): Takahashi T, Oono H, Inoue T, Boku S, Kako Y, Kitaichi Y, Kusumi I, Masui T, Nakagawa S, Suzuki K, Tanaka T, Koyama T, Radford MH
  • Journal Title: Neuro Endocrinol Lett 29 Pages: 351-8
  • Peer Reviewed
• [Journal Article] Effect of different challenge doses after repeated citalopram treatment on extracellular serotonin level in the medial prefrontal cortex : In vivo microdialysis study (2008)
  • Author(s): Muraki I, Inoue T, Hashimoto S, Izumi T, Koyama T
  • Journal Title: Psychiatry and Clinical Neurosciences 62 Pages: 568-574
  • Peer Reviewed
• [Journal Article] Pharmacokinetic interaction between tandospirone and fluvoxamine in the rat contextual conditioned fear stress model and its functional consequence : Involvement of cytochrome P450 3A4 (2008)
  • Author(s): Nishikawa H, Inoue T, Masui T, Izumi T, Nakagawa S, Koyama T
  • Journal Title: Involvement of cytochrome P450 3A4. Psychiatry and Clinical Neurosciences 62 Pages: 591-596
  • Peer Reviewed
• [Journal Article] SSRI・SNRI単剤にて寛解に至らなかった単極性うつ病患者における第二選択治療の有効性に関する調査研究 (2008)
  • Author(s): 新出泰士,中島幸治,北市雄士、中川 伸、井上 猛、小山 司
  • Journal Title: 臨床精神薬理 11 Pages: 1887-1898
  • Peer Reviewed
• [Journal Article] SSRIの作用標的としての扁桃体. 特集「扁桃体-情動脳と社会脳」 (2008)
  • Author(s): 井上 猛、北市雄士、小山 司
  • Journal Title: Clinical Neuroscience 26 Pages: 422-424
• [Journal Article] Changes in amygdala neural activity that occur with the extinction of context-dependent conditioned fear stress (2008)
  • Author(s): Izumi T, Inoue T, Kato A, Kitaichi Y, Nakagawa S, Koyama T
  • Journal Title: Pharmacol. Biochem. Behay. 90 Pages: 297-304
  • Peer Reviewed
• [Journal Article] Pharmacokinetic interaction between tandospirone and fluvoxamine in the rat contextual conditioned fear stress model and its functional conseouence : Involvement of cytochrome P450 3A4 (2008)
  • Author(s): Nishikawa H, Inoue T, Masui T, Izami T, Nakagawa S, Koyama T
  • Journal Title: Psychiatry and Clinical Neurosciences 62 Pages: 591-596
  • Peer Reviewed
• [Journal Article] Effect of co-administration of the selective 5-HT1A receptor antagonist WAY 100, 635 and selective 5-HT1B/1D receptor antagonist GR 127, 935 on anxiolytic effect of citalopram in conditioned fear stress in the rat. (2008)
  • Author(s): Muraki I
  • Journal Title: Eur J Pharmacol. (in press)
  • Peer Reviewed
• [Journal Article] Effects of cytochrome P450 (CYP) 3A4 inhibitors on the anxiolytic action of tandospirone in rat contextual conditioned fear (2007)
  • Author(s): Nishikawa H, Inoue T, Masui T, Izumi T, Koyama T
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry 31 Pages: 926-31
  • Peer Reviewed
• [Journal Article] Synergistic effects of tandospirone and selective serotonin reuptake inhibitors on the contextual conditioned fear stress response in rats (2007)
  • Author(s): Nishikawa H, Inoue T, Izumi T, Koyama T
  • Journal Title: Eur Neuropsychopharmacol 17 Pages: 643-650
  • Peer Reviewed
• [Journal Article] Effects of lithium on brain glucose metabolism in healthy men (2007)
  • Author(s): Kohno T, Shiga T, Toyomaki A, Kusumi I, Matsuyama T, Inoue T, Katoh C, Koyama T, Tamaki N
  • Journal Title: J Clin Psychopharmacol 27 Pages: 698-702
  • Peer Reviewed
• [Journal Article] Effects of cytochrome P450(CYP)3A4 inhibitors on the anxiolytic action of tandospirone in rat contextual conditioned fear. (2007)
  • Author(s): Nishikawa H
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry 31 Pages: 926-931
  • Peer Reviewed
• [Journal Article] Synergistic effects of tandospirone and selective serotonin reuptake inhibitors on the contextual conditioned fear stress response in rats. (2007)
  • Author(s): Nishikawa H
  • Journal Title: Eur Neuropsychopharmacol. 17 Pages: 643-650
  • Peer Reviewed
• [Presentation] 不安障害における扁桃体セロトニンの役割(シンポジウム) (2008)
  • Author(s): 井上 猛
  • Organizer: 第49回日本心身医学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2008-06-13
• [Presentation] 不安障害における扁桃体セロトニンの役割 (2008)
  • Author(s): 井上猛
  • Organizer: 第49回日本心身医学会総会シンポジウム「脳科学による心身症の解明」
  • Place of Presentation: 札幌(札幌コンベンションセンター)
  • Year and Date: 2008-06-13
• [Presentation] 恐怖条件付けにおける扁桃体セロトニンの役割(シンポジウム) (2007)
  • Author(s): 井上 猛
  • Organizer: 第29回日本生物学的精神医学会、第37回日本神経精神薬理学会合同年会
  • Place of Presentation: 札幌
  • Year and Date: 2007-07-11
• [Presentation] 恐怖条件付けにおける扁桃体セロトニンの役割. (2007)
  • Author(s): 井上 猛
  • Organizer: 第29回日本生物学的精神医学会シンポジウム「ストレス関連動物モデルの神経科学」
  • Place of Presentation: 札幌
  • Year and Date: 2007-07-11
• [Book] 難治性うつ病.「気分障害」(上島国利、樋口輝彦、野村総一郎、大野 裕、神庭重信、尾崎紀夫編集) (2008)
  • Author(s): 井上 猛、小山 司
  • Publisher: 医学書院、東京
• [Book] ドパミン・アゴニストと甲状腺剤の双極性障害治療への応用. 中山書店「専門医のための精神科臨床リュミエール : 双極性障害」 (2008)
  • Author(s): 井上 猛、小山 司
  • Publisher: 中山書店、東京
• [Remarks]
  • URL: http://www.med.hokudai.ac.jp/%7Epsy-w/index.html
• [Remarks]
  • URL: http://www.med.hokudai.ac.jp/%7Epsy-w/index.html