A study to clarify the role of neurocircuitry of emotional stress for the pathogenesis of mood disorders

• Project/Area Number: 21591478
• 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 北海道大学, 北海道大学病院, 講師 (70250438)
• Co-Investigator(Kenkyū-buntansha): NAKAGAWA Shin 北海道大学, 北海道大学病院, 講師 (60360905)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• 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薬(SSRI) / SSRI / 恐怖条件付き

Research Abstract

We clarified the mechanism of therapeutic drugs for mood disorders from an aspect of neurocircuitry by using a conditioned fear stress model, an animal model of emotional stress. We investigated the drugs to reduce or potentiate the effect of new antidepressants, such as SSRI, SNRI and mirtazapine, on anxiety behavior and neurotransmitters. Furthermore, we showed an important role of glutamatergic neurons in the basal nucleus of the amygdala for fear conditioning.

Research Products

• [Journal Article] Noradrenaline increases neural precursor cells derived from adult rat dentate gyrus through beta2 receptor (2012)
  • Author(s): Masuda T, Nakagawa S, Boku S, Nishikawa H, Takamura N, Kato A, Inoue T, Koyama T
  • Journal Title: Neuropsychopharmacol Biol Psychiatry Volume: 36 Pages: 44-51
  • Peer Reviewed
• [Journal Article] Effects of combined treatment with clorgyline and selegiline on extracellular noradrenaline and serotonin levels. Acta Neuropsychiatr (2012)
  • Author(s): Kitaichi Y, Inoue T, Nakagawa S, Boku S and Koyama T
  • Journal Title: Accepted manuscript online Volume: (in press) Issue: 6 Pages: 369-373
  • DOI: 10.1111/j.1601-5215.2012.00652.x
  • Peer Reviewed
• [Journal Article] Mood stabilizers commonly restore staurosporine-induced increase of p53 expression and following decrease of Bcl-2 expression in SH-SY5Y cells (2012)
  • Author(s): Song N, Boku S, Nakagawa S, Kato A, Toda H, Takamura N, Omiya Y, Kitaichi Y, Inoue T, Koyama T
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry
  • NAID: 120004857013
  • Peer Reviewed
• [Journal Article] prevents the anxiolytic-like effect of citalopram in rat contextual conditioned fear stress model (2012)
  • Author(s): Masuda T, Nishikawa H, Inoue T, Toda H, Nakagawa S, Boku S, Koyama T
  • Journal Title: Acta Neuropsychiatr. Accepted manuscript online Volume: 25 Issue: 2 Pages: 77-84
  • DOI: 10.1111/j.1601-5215.2012.00669.x
  • Peer Reviewed
• [Journal Article] 不安障害(特集生物学的精神医学の進歩) (2012)
  • Author(s): 井上猛、小山司
  • Journal Title: BRAIN and NERVE Volume: 64(2) Pages: 131-138
  • NAID: 40019196564
• [Journal Article] Noradrenaline increases neural precursor cells derived from adult rat dentate gyrus through beta2 receptor (2012)
  • Author(s): Masuda T, et al.
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 36 Issue: 1 Pages: 44-51
  • DOI: 10.1016/j.pnpbp.2011.08.019
  • Peer Reviewed
• [Journal Article] Mood stabilizers commonly restore staurosporine-induced increase of p53 expression and following decrease of Bcl-2 expression in SH-SY5Y cells (2012)
  • Author(s): Song N, et al.
  • Journal Title: Prog Neuropsychophamacol Biol Psychiatry Volume: (in press) Issue: 2 Pages: 183-189
  • DOI: 10.1016/j.pnpbp.2012.03.006
  • Peer Reviewed
• [Journal Article] Sertraline Treatment of Patients with Major Depressive Disorder who Failed Initial Treatment with Paroxetine or Fluvoxamine (2012)
  • Author(s): Inoue T, et al.
  • Journal Title: Prog Neuropsychophamacol Biol Psychiatry Volume: (in press) Issue: 2 Pages: 223-227
  • DOI: 10.1016/j.pnpbp.2012.04.001
  • Peer Reviewed
• [Journal Article] Effects of mood stabilizers on adult dentate gyrus-derived neural precursor cells (2011)
  • Author(s): Boku S, Nakagawa S, Masuda T, Nishikawa H, Kato A, Toda H, Song N, Kitaichi Y, Inoue T, Koyama T
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 35 Pages: 111-117
  • NAID: 120004856983
  • Peer Reviewed
• [Journal Article] Lamotrigine blocks apoptosis induced by repeated administration of high-dose methamphetamine in the medial prefrontal cortex of rats (2011)
  • Author(s): Nakato Y, Abekawa T, Ito K, Inoue T, Koyama T
  • Journal Title: Neurosci Lett Volume: 490 Pages: 161-164
  • NAID: 120003354965
  • Peer Reviewed
• [Journal Article] Retrieval of conditioned fear activates the basolateral and intercalated nucleus of amygdala (2011)
  • Author(s): Izumi T, Boku S, Shinmin W, Inoue T, Konno K, Yamaguchi T, Yoshida T, Matsumoto M, Watanabe M, Koyama T, Yoshioka M.
  • Journal Title: J Neurosci Res Volume: 89(5) Pages: 773-790
  • Peer Reviewed
• [Journal Article] SSRIs and conditioned fear (2011)
  • Author(s): Inoue T, Kitaichi Y, Koyama T
  • Journal Title: Neuropsychopharmacol Biol Psychiatry Volume: 35 Pages: 1810-1819
  • Peer Reviewed
• [Journal Article] Lamotrigine blocks repeated high-dose methamphetamine-induced behavioral sensitization to dizocilpine (MK-801), but not methamphetamine in rats (2011)
  • Author(s): Nakato Y, Abekawa T, Inoue T, Ito K, Koyama T.
  • Journal Title: Neurosci Lett Volume: 504(2) Pages: 131-4
  • NAID: 120003413070
  • Peer Reviewed
• [Journal Article] SSRIs and conditioned fear (2011)
  • Author(s): Inoue T, et al.
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 35 Issue: 8 Pages: 1810-1819
  • DOI: 10.1016/j.pnpbp.2011.09.002
  • Peer Reviewed
• [Journal Article] DNA methylation profiles of the brain-derived neurotrophic factor (BDNF) gene as a potent diagnostic biomarker in major depression (2011)
  • Author(s): Fuchikami M, et al.
  • Journal Title: PLoS One Volume: 6 Issue: 8 Pages: e23881-e23881
  • DOI: 10.1371/journal.pone.0023881
  • Peer Reviewed
• [Journal Article] Lamotrigine blocks repeated high-dose methamphetamine-induced behavioral sensitization to dizocilpine (MK-801), but not methamphetamine in rats (2011)
  • Author(s): Nakato Y, et al.
  • Journal Title: Neurosci Lett Volume: 504 Issue: 2 Pages: 131-4
  • DOI: 10.1016/j.neulet.2011.09.017
  • Peer Reviewed
• [Journal Article] Effects of mood stabilizers on adult dentate gyrus-derived neural precursor cells. (2011)
  • Author(s): Boku S, et al.
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 35 Pages: 111-117
  • Peer Reviewed
• [Journal Article] Lamotrigine blocks apoptosis induced by repeated administration of high-dose methamphetamine in the medial prefrontal cortex of rats. (2011)
  • Author(s): Nakato Y, et al.
  • Journal Title: Neurosci Lett Volume: 490 Pages: 161-164
  • Peer Reviewed
• [Journal Article] Retrieval of conditioned fear activates the basolateral and intercalated nucleus of amygdala. (2011)
  • Author(s): Izumi T, et al.
  • Journal Title: J Neurosci Res Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Olanzapine augmentation of milnacipran for stage 2 treatment-resistant major depression : an open study. (2011)
  • Author(s): Boku S, et al.
  • Journal Title: Human Psychopharmacology : Clinical and Experimental Volume: (in press,in press)
  • Peer Reviewed
• [Journal Article] Long-term naturalistic follow-up of lithium augmentation : relevance to bipolarity. (2011)
  • Author(s): Inoue T, et al.
  • Journal Title: J Affect Disord Volume: 129 Pages: 64-67
  • Peer Reviewed
• [Journal Article] Combined treatment with MAO-A inhibitor and MAO-B inhibitor increases extracellular noradrenaline levels more than MAO-A inhibitor alone through increases in β-phenylethylamine (2010)
  • Author(s): Kitaichi Y, Inoue T, Nakagawa S, Boku S, Izumi T, Koyama T
  • Journal Title: Eur J Pharmacol Volume: 637(1-3) Pages: 77-82
  • NAID: 120002261718
  • Peer Reviewed
• [Journal Article] a glycine transporter-1 (GlyT1) inhibitor, attenuates acquisition and expression of contextual conditioned fear in rats (2010)
  • Author(s): Nishikawa H, Inoue T, Izumi T, Nakagawa S, Koyama T
  • Journal Title: Behav Pharmacol Volume: 21(5-6) Pages: 576-9
  • Peer Reviewed
• [Journal Article] Lamotrigine blocks the initiation and expression of repeated high-dose methamphetamine-induced prepulse inhibition deficit in rats (2010)
  • Author(s): Nakato Y, Abekawa T, Ito K, Inoue T, Koyama T
  • Journal Title: Neurosci Lett Volume: 481 Pages: 183-187
  • NAID: 120002386834
  • Peer Reviewed
• [Journal Article] Sertraline increases extracellular levels not only of serotonin, but also of dopamine in the nucleus accumbens and striatum of rats (2010)
  • Author(s): Kitaichi Y, Inoue T, Nakagawa S, Boku S, Kakuta A, Izumi T, Koyama T
  • Journal Title: Eur J Pharmacol Volume: 647 Pages: 90-96
  • Peer Reviewed
• [Journal Article] 痛覚による恐怖条件付けにおけるセロトニンの機能的役割 (2010)
  • Author(s): 井上猛、小山司
  • Journal Title: 医学のあゆみ Volume: 232(1) Pages: 75-79
• [Journal Article] Combined treatment with MAO-A inhibitor and MAO-B inhibitor increases extracellular noradrenaline levels more than MAO-A inhibitor alone through increases in β-phenylethylamine. (2010)
  • Author(s): Kitaichi Y, et al.
  • Journal Title: Eur J Pharmacol Volume: 637 Pages: 77-82
  • Peer Reviewed
• [Journal Article] SSR504734, a glycine transporter-1 (G1yT1) inhibitor, attenuates acquisition and expression of contextual conditioned fear in rats. (2010)
  • Author(s): Nishikawa H, et al.
  • Journal Title: Behav Pharmacol Volume: 21 Pages: 576-579
  • Peer Reviewed
• [Journal Article] Lamotrigine blocks the initiation and expression of repeated high-dose methamphetamine-induced prepulse inhibition deficit in rats. (2010)
  • Author(s): Nakato Y, et al.
  • Journal Title: Neurosci Lett Volume: 481 Pages: 183-187
  • Peer Reviewed
• [Journal Article] Pramipexole for stage 2 treatment-resistant major depression : an open study. (2010)
  • Author(s): Inoue T, et al.
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 34 Pages: 1446-1449
  • Peer Reviewed
• [Journal Article] Sertraline increases extracellular levels not only of serotonin, but also of dopamine in the nucleus accumbens and striatum of rats. (2010)
  • Author(s): Kitaichi Y, et al.
  • Journal Title: Eur J Pharmacol. Volume: 647 Pages: 90-96
  • Peer Reviewed
• [Journal Article] Depression and major depressive disorder in patients with Parkinson's disease (2010)
  • Author(s): Inoue T, et al.
  • Journal Title: Movement Disorders 25 Pages: 44-49
  • Peer Reviewed
• [Journal Article] 痛覚による恐怖条件付けにおけるセロトニンの機能的役割 (2010)
  • Author(s): 井上猛、小山司
  • Journal Title: 医学のあゆみ 232 Pages: 75-79
• [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 Volume: 49(4) Pages: 291-297
• [Journal Article] 不安障害における扁桃体セロトニンの役割 (2009)
  • Author(s): 井上猛、小山司
  • Journal Title: 心身医学 49 Pages: 291-297
• [Presentation] Rho-associated coiled-coil kinase (ROCK2) regulates bFGF-induced proliferation of SH-SY5Y cells through GSK-3 βand β-catenin pathway (2011)
  • Author(s): Boku S, et al.
  • Organizer: Society for Neuroscience 41th annual meeting
  • Place of Presentation: Walter E. Washington Convention Center (USA)
  • Year and Date: 2011-11-12
• [Presentation] Involvement of CaM kinase IV in the action of antidepressant treatment (2011)
  • Author(s): Nakagawa S, et al.
  • Organizer: Society for Neuroscience 41th annual meeting
  • Place of Presentation: Walter E. Washington Convention Center (USA)
  • Year and Date: 2011-11-12
• [Presentation] Emotional memory and animal models of psychiatric disorders : an overview and learning-based animal models of anxiety (2011)
  • Author(s): Inoue T
  • Organizer: 2nd Congress of Asian College of Neuropsychopharmacology
  • Place of Presentation: Grand Hilton Seoul Hotel (Korea)(招待講演)
  • Year and Date: 2011-09-23
• [Presentation] an overview and learning-based animal models of anxiety (2011)
  • Author(s): Inoue T
  • Organizer: (Symposium) 2nd Congress of Asian College of Neuropsychopharmacology
  • Place of Presentation: Seoul, Korea
• [Presentation] Dopamine increases the proliferation of adult rat dentate gyrus-derived neural precursor cells through dopamine Dl-like receptors. (2010)
  • Author(s): Takamura N, et al.
  • Organizer: 40th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2010-11-17
• [Presentation] Influence of early-life stress on behavior, HPA axis activity, gene expressions and hippocampal neurogenesis in adulthood rats. (2010)
  • Author(s): Toda H, et al.
  • Organizer: 40th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2010-11-17
• [Presentation] Maternal separation attenuates retinoic acid-induced neural differentiation of adult rat dentate gyrus-derived neural precursor cells through decreasing the expression of retinoic acid receptor α (2010)
  • Author(s): Boku S, et al.
  • Organizer: 40th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2010-11-17
• [Presentation] Maternal separation stress and vulnerability to anxiety behavior in rats (2010)
  • Author(s): Toda H, Nakagawa S, Boku S, Kato A, Takamura N, Song N, Inoue T, Koyama T
  • Organizer: 40th annual meeting of Society for Neuroscience
  • Place of Presentation: San Diego,USA
• [Presentation] Effect of co-administration of mirtazapine with citalop ram in rat contextual conditioned fear stress model. (2009)
  • Author(s): Inoue T, et al.
  • Organizer: 第19回日本臨床精神神経薬理学会・第39回日本神経精神薬理学会・1stAsCNP合同年会
  • Place of Presentation: 国立京都国際会館(京都)
  • Year and Date: 2009-11-14
• [Presentation] Effect of co-administration of mirtazapine with citalopram in rat contextual conditioned fear stress model (2009)
  • Author(s): Inoue T, Masuda T, Takamura N, Nakagawa S, Boku S, Toda H, Koyama T
  • Organizer: 第19回日本臨床精神神経薬理学会・第39回日本神経精神薬理学会・The 1st Meeting of the Asian College of Neuropsychopharmacology(AsCNP)合同年会
  • Place of Presentation: 国立京都国際会館(京都)
• [Presentation] Dexamethasone /corticotrophin releasing hormone test in maternal separation stress models (2009)
  • Author(s): Toda H, Nakagawa S, Boku S, Song N, Kato A, Inoue T, Koyama T
  • Organizer: 39th Annual Meeting of Society for Neuroscience
  • Place of Presentation: Chicago, USA
• [Book] 気分障害の薬理・生化学-総括と新たなる挑戦- (2012)
  • Author(s): 井上 猛
  • Publisher: 医薬ジャーナル、東京(印刷中)
• [Book] 精神科領域からみた心身症 (2011)
  • Author(s): 井上猛、小山司
  • Publisher: 中山書店、東京(石津宏編)