| Project/Area Number |
10670915
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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) |
MINATOGAWA Yukiko Saitama Medical School, School of Medicine, Research Associate, 医学部, 助手 (60146272)
SUETSUGI Masatomo Yamaguchi University, School of Medicine, Research Associate, 医学部, 助手 (40294631)
KANEYUKI Hiroshi Yamaguchi University, Hospital, Assistant Professor, 医学部・附属病院, 講師 (30263784)
IIDA Atsufumi Saitama Medical School, School of Medicine, Research Associate, 医学部, 助手 (40255089)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1998: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | stress vulnerability / Wistar Kyoto rats / hypothalamus-pituitary-adrenal axis / c-fos mRNA / habituation / corticotropin releasing hormone / tyrosine hydroxylase / serotonin transporter / 視床下部-下垂体-副腎体 / うつ病モデル / Wistar Kyoto ラット / コルチコトロピン遊離促進ホルモン / バソプレシン / エンケファリン / 視床下部室傍核 |
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| Research Abstract |
Because of induction of depression by psycho-social stress, patients with depression have been thought to have stress vulnerability. Thus, animal with stress vulnerability should be ideal models for depression. Wistar Kyoto (WKY) rats, who are sensitive and emotional to acute stress compared to Wistar rats, are possible candidate for an animal model for depression with stress vulnerability.
To examine the vulnerability of WKY rats to repeated stress, we investigated stress responses of hypothlamus-pituitary-adrenal (HPA) axis and of emotional behavior. Well-habituated Wistar rats showed decrement of plasma corticosterone level after reaching to the peak level, that is "enhanced negative-feedback", and shortening of freezing time after stress with repeated stress, whereas WKY rats did not show such habituation phenomena. These results indicate the vulnerability of WKY rats to repeated stress.
While acute stress induced c-fos mRNA expression in various brain regions, these stress-induced c
… More
-fos mRNA expression was reduced dramatically after repeated stress in well-habituated Wistar rats. WKY rats showed the same reduction of the stress-induced c-fos mRNA expression in various brain regions, such as periventral nucleus of the hypothalamus (PVN), septum, amygdala, cerebral cortex, locus coeruleus (LC) and raphe nucleus. As for stress-induced expression of late response genes, such as corticotropin releasing hormone (CRH) gene in the PVN and tyrosine hydroxylase (TH) gene in the LC, both Wistar and WKY rats also showed similar habituation to repeated stress. Acute stress enhanced expression of CRH and TH genes expression, whereas the stress-induced expression of these genes were diminished with increased basal levels of gene expression after repeated stress. The expression of 5HTT gene in the raphe nucleus was not changed by both acute and repeated stress in Wistar and WKY rats. These results are oppisite to those of HPA axis and stress-induced anxious behavior, those indicate the stress vulnerability of WKY rats. To elucidate the reasons of this contradiction, it is required to examine the alterations of gene expression of glucocorticoid receptors and Vasopressin in the PVN and the hippocampus of WKY rats. Less
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