1995 Fiscal Year Final Research Report Summary
Strategies for the study of the disinhibition of Hypothalamic-Pituitary-Adrenal axis in affective disorders, using prenatal stress model.
| Project/Area Number |
06670994
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Psychiatric science
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| Research Institution | Department of Neuropsychiatry, Gunma University |
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Principal Investigator |
MIKUNI Masahiko Depertment of Neuropsychiatry, Gunma University, 医学部, 助教授 (00125353)
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| Co-Investigator(Kenkyū-buntansha) |
IDA I Depertment of Neuropsychiatry, Gunma University, 医学部, 助手 (50251103)
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| Project Period (FY) |
1994 – 1995
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| Keywords | prenatal stress / neuronal plasiticity / hypothalamo-pituitary-adrenal axis |
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| 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.
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[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)
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