| Project/Area Number |
12670942
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Yamaguchi University |
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Principal Investigator |
WATANABE Yoshifumi Yamaguchi University, School of Medicine, Professor, 医学部, 教授 (90182964)
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| Co-Investigator(Kenkyū-buntansha) |
DAIRAKU Yoshikazu Yamaguchi University, Hospital, clinical fellow, 医学部・附属病院, 医員(臨床)
SUETUGI Masatomo Yamaguchi University, School of Medicine, research assosiate, 医学部, 助手 (40294631)
HASHIMOTO Manabu Yamaguchi University, Hospital, research assosiate, 医学部・附属病院, 助手 (80314805)
TSUTIYA Ken Yamaguchi University, Hospital, clinical fellow, 医学部, 医員(臨床)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | model for depression / Fisher344 rats / stress vulnerability / Hypothalamo - pituitary - adrenal axis / chronic stress / c - fos / antidepressants / periventricular nucleus of hypothalamus / コルチコステロン |
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| Research Abstract |
The aim of this study is to investigate the possibility of the Fischer344 rats, who have been confirmed to be vulnerable to chronic stress, for a suitable animal model for depression. We investigated the effects of long-term administration of an antidepressant, imipramine, on maladaptation of Fischer344 rats to chronic stress. In this study, we used stress-responses of Hypothalamo-pituitary-adrenal (HPA) axis (blood concentration of glucocorticoids (GC)) and expression of c-fos mRNA as indices of stress adaptation.
Without antidepressant administration, the pattern of blood concentration alteration of GC during stress was not changed with repeated restraint stress for 13 days. As for stress response of c-fos mRNA expression, Fischer344 rats showed delayed adapted change, such as a reduction of stress-induced increase in expression of c-fos mRNA, after repeated restraint stress for seven days. Usually, this adapted change of c-fos mRNA is revealed after three days stress in normal adaptation.
Long-term administration of imipramine prevented the HPA axis of Fischer344 rats from maladaptaion to repeated stress, while maladaptation of c-fos mRNA expression of Fischer344 rats, which was revealed in paraventricular nucleus of hypothalamus, lateral nucleus of septum, and piriform cortex, was not corrected by long-term administration of imipramine. With long-term administration of imipramine, blood concentration of GC was decreased dramatically 60 min after the beginning of stress after seven days repeated stress, without an alteration of peak concentration at 30 min after the beginning of stress.
These results suggest the preventive effect of antidepressants on stress vulnerability of Fischer344 rats. Consequently, it is plausible that Fischer344 rats could be a suitable animal model for depression with congenital stress vulnerability.
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