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Strategies for the study of the disinhibition of Hypothalamic-Pituitary-Adrenal axis in affective disorders, using prenatal stress model.

Research Project

Project/Area Number 06670994
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Psychiatric science
Research InstitutionDepartment of Neuropsychiatry, Gunma University

Principal Investigator

MIKUNI Masahiko  Depertment of Neuropsychiatry, Gunma University, 医学部, 助教授 (00125353)

Co-Investigator(Kenkyū-buntansha) IDA I  Depertment of Neuropsychiatry, Gunma University, 医学部, 助手 (50251103)
飯島 幸生  群馬大学, 医学部・神経精神医学講座, 助手 (60251104)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1994: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordsprenatal stress / neuronal plasiticity / hypothalamo-pituitary-adrenal axis / ストレス脆弱性 / 強制水泳試験 / グルココルチコイド受容体 / 最初期遺伝子 / コルチコトロピン遊離促進ホルモン遺伝子
Research Abstract

In this study we have investigated whether animals prenatally exposed to mild stress produce the overactivity of Hypothalamo-Pituitary-Adrenal (HPA) axis and alterations of anxiety-or mood-related behaviors in the response to stressful stimuli as well as a deficit of monoaminergic activities in adult offspring, which are frequently seen in depression. The prenatal saline injection stress increased the corticosterone secretion to a significantly greater extent during conditioned fear stress in offspring at 7 and 28 weeks of age in comparison with controls. In addition, decreased entry numbers into open and closed arms in elevated plus maze for the first 5-min session were observed in the prenatally stressed groups, suggesting that prenatally stressed offspring were more anxious under the new environmental conditions than controls. A prolonged immobility duration in forced swimming test was also observed in the prenatally stressed adult offspring, indicating that the prenatally stressed offspring seemed to be susceptible to behavioral'despair'. On the other hand, the 5-hydroxytryptamine concentration in the hypothalamus from prenatally stressed offspring in adulthood was observed to be higher than controls, in contrast of unaltered serotonin metabolite, 5-hydroxyindoleacetic acid. This deficit of serotonergic activity may be one of the vulnerability factors, revealing overactivity of the HPA axis in the response to stressful stimuli. These results of endocrine response and altered behavioral activity under stressful conditions, and the deficit of serotonergic activity suggest that the prenatal saline injection stress model may have a face validity as an animal model of depression.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] T. Ogawa, M. Mikuni, et al.: "Periodic maternal deprivatiom alters stress response in adult offspring" Pharmacol. Biochem. & Behav.49. 961-967 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K. Maneoka, M. Mikuni, et al.: "Periodic maternal deprivation-induced potentiation of negative feedback sensitivity to glucocorticoid" Neuroscience Letters. 168. 89-92 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T. Ogawa, M. Mikuni, et al.: "Effects of the altered serotonergic signalling by" J. Neural Transmission. 96. 113-123 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H. Shinno, M. Mikuni, et al: "Metabotropic glutamate receptor in C6BU-1 glioma cell has NMDA receptor-ion channel complex-like properties" J. Neurochem.63. 1346-1353 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y. Niitsu, M. Mikuni, et al.: "Regulation of synapse density by 5-HT-2A receptor agonist and antagonist in the spinal cord of embryo" Neuroscience Letters. 195. 159-162 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K. Saitoh, M. Mikuni, et al.: "Serotonin-induced 5-HT-1A receptor desensitization" Neuroscience Letters. 199. 191-194 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masahiko Mikuni, et al.: "Serotonin in the Central Nervous System and Periphery, edited. by A. Takada and G. Curzon" Elsevier Science, 260 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 三国雅彦: "発達障害医学の進歩 No. 6、有馬正高、熊谷公明、原 仁編" 診断と治療社, 89 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tetsuo Ogawa, Masahiko Mikuni, Yasukazu Kuroda, Katsumasa Muneoka, Kazuhiro John Mori and Kiyohisa Takahashi: "Periodic maternal deprivation alters stress response in adult offspring : Potentiates the negative feedback regulation of restraint stress-induced adrenocortical response and reduces the frequencies of open field-induced behaviors." Pharmacology, Biochemistry & Behavior. 49. 961-967 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Katsumasa Muneoka, Masahiko Mikuni, Tetsuo Ogawa, Katsuki Kitera and Kiyohisa Takahashi: "Periodic maternal deprivation-induced Potentiation of negative feedback sensitivity to glucocorticoids to inhibit stress-induced adrenocortical response persists throughout the animal's life-span." Neuroscience Letters. 168. 89-92 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tetsuo Ogawa, Masahiko Mikuni, Yasukazu Kuroda, Katsumasa Muneoka, Kazuhiro John Mori and Kiyohisa Takahashi: "Effects of the altered serotonergic signalling by neonatal treatment with 5,7-dihydroxytryptamine, ritanserin or clomipramine on the adrenocortical stress response and the glucocorticoid receptor binding in the hippocampus in adult rats." J.Neural Transmission. 96. 113-123 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hideto Shinno, Masahiko Mikuni, Kazuko Saitoh, Urara Tomita, Shigeto Yamawaki and Kiyohisa Takahashi: "Metabotropic glutamate receptor in C6BU-1 glima cell has NMDA receptor-ion channel complex-like properties and interacts with serotonin-2 receptor-stimulated signal transduction." J.Neurochemistry. 63. 1346-1353 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoichi Niitsu, Shun Hamada, Kayoko Hamaguchi, Masahiko Mikuni, and Nobuo Okada: "Regulation of synapse density by 5-HT-2A receptor agonist and antagonist in the spinal cord of chicken embryo." Neuroscience Letters. 195. 159-162 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ariyuki Kagaya, Masahiko Mikuni, Y Okamoto, Shin-ichiro Muraoka, Nobumasa Motohashi, Shigeto Yamawaki and Kiyohisa Takahashi: "W-7 facilitates 5-HT-2A receptor-mediated intracellular calcium increase in human platelets." Pharmaceutical Science. 1. 141-143 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kazuko Saitoh, Masahiko Mikuni, Masaaki Ikeda, Chihiro Yamazaki, Urara Tomita, and Kiyohisa Takahashi: "Serotonin-induced 5-HT-1A receptor desensitization in C6BU-1 glioma cells transfected with 5-HT-1A receptor gene." Neuroscience Letters. 199. 191-194 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masahiko Mikuni, Katsuki Kitera, Kazuko, Saitoh, Chihiro Yamazaki, Hiroaki Okuyama, Takehiko Majima, Itsuro Ida, Yukio Iijima and Kiyohisa Takahashi: "Effects of prenatal stressful stimuli on serotonin content in the hypothalamus and pituitary-adrenal response to conditioned fear stress in adult offsping." In : Serotonin in the Central Nervous System and Periphery, ed.by A.Takada and G.Curzon, pp.81-87, Elsevier Science, Amsterdam. (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T. Ogawa, M. Mikuni, et al: "Periodic maternal deprivatiom alters stress response in adult offspring" Pharmacol. Biochem. & Behav.49. 961-967 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] K. Maneoka, M. Mikuni, et al: "Periodic maternal deprivatiom-induced potentiation of negative feedback sensitivity to glucocorticoid" Neuroscience Letters. 168. 89-92 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] T. Ogawa, M. Mikuni, et al: "Effects of the altered serotonergic signalling by" J. Neural Transmission. 96. 113-123 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] H. Shinno, M. Mikuni, et al: "Metabotropic glutamate receptor in C6BU-1 glioma cell has NMDA receptor-ion channel complex-like properties" J. Neurochem.63. 1346-1353 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Y. Niitsu, M. Mikuni, et al: "Regulation of synapse density by 5-HT-2A receptor agonist and antagonist in the spinal cord of embryo" Neuroscience Letters. 195. 159-162 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] K. Saitoh, M. Mikuni, et al: "Serotonin-induced 5-HT-1A receptor desensitization" Neuroscience Letters. 199. 191-194 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Masahiko Mikuni, et al: "Serotonin in the Central Nervous System and Periphery, edited. by A. Takada and G. Curzon" Elsevier Science, 260 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 三国雅彦: "発達障害医学の進歩 No. 6、有馬正高、熊谷公明、原 仁編" 診断と治療社, 89 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tetsuo Ogawa,Masahiko Mikuni,: "Periodic matemal deprivation alters stress response in adult offspring:Potentiates the negative feedback regulation of restraint stress-induced adrenocortical response and reduces the frequencies of open field-induced behaviors." Pharmacology,Biochemistry & Behavior. 49. 961-967 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Katsumasa Muneoka,: "Periodic matermal deprivation-induced potentiation of negative feedback sensitivity to glucocorticoids to inhibit stress-induced adrenocortical response persists throughout the animal's life-span." Neuroscience Letters. 168. 89-92 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Tetsuo Ogawa,Masahiko Mikuni,: "Effects of the altered serotonergic signalling by neonatal treatment with 5,7-dihydroxytryptamine,ritanserin or clomipramine on the adrenocortical stress response and the glucocorticoid receptor binding in the hippocampus in adult rats." J.Neural Transmission. 96. 113-123 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hideto Shinno,Masahiko Mikuni,: "Metabotropic glutamate receptor in C6BU-1 glioma cell has NMDA receptor-ion channel complex-like properties and interacts with serotonin-2 receptor-stimulated signal transduction." J.Neurochemistry. 63. 1346-1353 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 三国雅彦: "不安の制御物質とその神経回路網" 脳と精神の医学. 5. 253-261 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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