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Study on the role of emotional stress for the pathogenesis of psychiatric disorders. -To clarify the relationship between emotional stress and central monoaminergic/peptidergic neural systems using animal models-

Research Project

Project/Area Number 09470205
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

KOYAMA Tsukasa  Hokkaido Univ.Grad.School of Medicine, Prof., 大学院・医学研究科, 教授 (10113557)

Co-Investigator(Kenkyū-buntansha) INOUE Takeshi  Hokkaido University, Medical Hospital, Lec., 医学部・附属病院, 講師 (70250438)
Project Period (FY) 1997 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1997: ¥8,300,000 (Direct Cost: ¥8,300,000)
KeywordsAnxiety / Serotonin / SSRI / Monoamine oxidase inhibitor / amygdala / Dopamine / mRNA / Lithium / SSR1 / 精神分裂症 / うつ病 / 情動ストレス / コレシストキニン / 精神分裂病
Research Abstract

The purpose of this study is to clarify the effect of conditioned fear stress on central monoaminergic and peptidergic systems using in vivo microdialysis, radioimmunoassay, in situ hybridization, and Northern Blot in discrete brain regions and to examine functional localization of neural systems.
1) Selective serotonin reuptake inhibitors (SSRIs) reduced conditioned freezing, an index of anxiety, and these anxiolytic effects were enhanced by subchronic lithium pretreatment at the therapeutic plasma lithium levels.
The anxiolytic effects of serotonin1A agonists were also enhanced by subchronic lithium pretreatment. In vivo microdialysis studies showed that subchronic lithium treatment increased basal levels of extracellular serotonin and induced additive effects on SSRI-induced increases in extracellular serotonin.
2) The anxiolytic effects of monoamine oxidase inhibitors (MAOIs) were tested in the conditioned fear model. MAO-A inhibitors or MAO-B inhibitors did not induce anxiolytic effects, but non-selective MAOIs and the combination of MAO-A and MAO-B inhibitors were anxiolytic. In vivo microdialysis studies showed that the combination of MAO-A and MAO-B inhibitors induced more increases in extracellular serotonin than either inhibitor alone did.
3) Lithium and SSRI treatment increased the level of dopamine2 receptor mRNA and the transcription rate of the dopamine2 receptor gene in the rat striatum.

Report

(5 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Xiao-bai Li: "Effect of chronic administration of flesinoxan and fluvoxamine on freezing behavior induced by conditioned fear"European Journal of Pharmacology. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ihoko Muraki: "Effect of subchronic lithium treatment on citalopram-induced increases in extracellular concentrations of serotonin in the medial prefrontal cortex."Journal of Neurochemistry. 76. 490-497 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kensuke Kamada: "Effects of citalopram on dopamine D2 receptor expression in the rat brain striatum."Journal of Neural Transmission. 108. 321-334 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kensuke Kameda: "Effects of citalopram on dopamine D2 receptor expression in the rat brain striatum."Journal of Molecular Neuroscience. 14. 77-86 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yuji Maki: "Monoamine oxidase Inhibitors reduce conditioned fear stress-induced freezing behavior in rats."European Journal of Pharmacology. 406. 411-418 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takeshi Inoue: "Effect of the dopamine D1/5 antagonist SCH 23390 on the acquisition of conditioned fear."Pharmacology, Biochemistry and Behavior. 66. 573-578 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takeshi Izumi: "Effects of the benzodiazepine antagonist flumazenil on conditioned fear stress in rats."Progress in Neuro-Psychopharmacology and Biological Psychiatry. 23. 1247-1258 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ihoko Muraki: "Effect of subchronic lithium carbonate treatment on anxiolytic-like effect of citalopram and MKC-242 in conditioned fear stress in the rat."European Journal of Pharmacology. 383. 223-229 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shinji Hashimoto: "Effects of conditioned fear stress on serotonin neurotransmission and freezing behavior in rats."European Journal of Pharmacology. 378. 23-30 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shinji Hashimoto: "The effects of the co-administration of 5-HT1A receptor antagonists with an SSRI in conditioned fear stress-induced freezing behavior."Pharmacology, Biochemistry and Behavior. 58. 471-475 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takeshi Inoue: "Affective Minds (Serotonergic neurotransmission and defensive freezing in the conditioned fear stress paradigm.)"Elsevier Science, Amsterdam. pp91-100 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Xiao-bai Li: "Effect of chronic administration of flesinoxan and fluvoxamine on freezing behavior induced by conditioned fear"European Journal of Pharmacology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kensuke Kameda: "Effects of citalopram on dopamine D2 receptor expression in the rat brain striatum."Journal of Neural Transmission. 108. 321-334 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ihoko Muraki: "Effect of subchronic lithium treatment on citalopram-induced increases in extracellular concentrations of serotonin in the medial prefrontal cortex."Journal of Neurochemistry. 76. 490-497 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kensuke Kameda: "Effects of citalopram on dopamine D2 receptor expression in the rat brain striatum."Journal of Molecular Neuroscience. 14. 77-86 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yuji Maki: "Monoamine oxidase Inhibitors reduce conditioned fear stress-induced freezing behavior in rats."European Journal of Pharmacology. 406. 411-418 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takeshi Inoue: "Effect of the dopamine D1/5 antagonist SCH 23390 on the acquisition of conditioned fear."Pharmacology, Biochemistry and Behavior. 66. 573-578 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takeshi Izumi: "Effects of the benzodiazepine antagonist flumazenil on conditioned fear stress in rats ."Progress in Neuro-Psychopharmacology and Biological Psychiatry. 23. 1247-1258 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ihoko Muraki: "Effect of subchronic lithium carbonate treatment on anxiolytic-like effect of citalopram and MKC-242 in conditioned fear stress in the rat."European Journal of Pharmacology. 383. 223-229 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shinji Hashimoto: "Effects of conditioned fear stress on serotonin neurotransmission and freezing behavior in rats."European Journal of Pharmacology. 378. 23-30 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shinji Hashimoto: "The effects of the co-administration of 5 -HT1A receptor antagonists with an SSRI in conditioned fear stress-induced freezing behavior."Pharmacology, Biochemistry and Behavior. 58. 471-475 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takeshi Inoue: "Serotonergic neurotransmission and defensive freezing in the conditioned fear stress paradigm, In : Affective Minds"Elsevier Science, Amsterdam. 91-100 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 井上猛: "不安・恐怖のセロトニン仮説."脳と精神の医学. 11(4). 341-351 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yuji Maki: "Monoamine oxidase Inhibitors reduce conditioned fear stress-induced freezing behavior in rats."Eurpean Journal of Pharmacology. 406. 411-418 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ihoko Muraki: "Effect of subchronic lithium treatment on citalopram-induced increases in extracellular concentrations of serotonin in the medial prefrontal cortex."Journal of Neurochmemistry. 76(2). 490-497 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kensuke Kameda: "Effects of citalopram on dopamine D2 receptor expression in the rat brain striatum."Journal of Molecular Neuroscience. 14. 77-86 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takeshi Inoue: "Effect of the dopamine D1/5 antagonist SCH23390 on the acquisition of conitioned fear"Pharmacology Biochemistry and Behavior. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 井上 猛: "ヒトの不安・恐怖における扁桃体の役割"脳の科学. 21(a). 1011-1015 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ihoko Muraki: "Effect of subchronic lithium carbonate treatment on anxiolytic-like effect of citalopram and MKC-242 in conditioned fear stress in the rat"European Journal of Pharmacology. 383(3). 223-229 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takeshi Inoue: "Affective Mind. Sentonevgor neurotransmission and clefensive freening in the conditioned fear paradigm"Elsevie.

    • Related Report
      1999 Annual Research Report
  • [Publications] 井上 猛: "恐怖症の仮説:生物モデル(1)セロトニン仮説" 心の臨床アラカルト. 17(Suppl). 205-208 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] S.Hashimoto: "The effects of the co-administration of 5-HT1A receptor antagonists with an SSRI in conditioned fear stress-induced freezing behavior" Pharmacology, Biochemistry and Behavior. 58(2). 471-475 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 井上 猛: "不安の動物モデルと精神薬理学-SSRIの抗不安作用を中心に-" 神経研究の進歩. 41(4). 551-561 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 井上 猛: "不安障害の生物学" 臨床精神薬理. 1(5). 397-405 (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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