Stress vulnerability in Wistar Kyoto rats : possibility of an animal model for depression.

Wistar京都大鼠的应激脆弱性：抑郁症动物模型的可能性。

基本信息

批准号：
10670915
负责人：
WATANABE Yoshifumi
金额：
$ 2.05万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

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

由于心理社会压力会诱发抑郁症，抑郁症患者被认为具有应激脆弱性，因此，具有应激脆弱性的动物应该是对急性应激敏感且情绪化的抑郁症大鼠。与 Wistar 大鼠相比，WKY 大鼠可能是具有应激脆弱性的抑郁症动物模型的候选者。为了检查 WKY 大鼠对重复应激的脆弱性，我们研究了下丘脑-垂体-肾上腺 (HPA) 轴和情绪行为的应激反应。习惯了Wistar大鼠在达到峰值水平后表现出血浆皮质酮水平下降，即“增强的负反馈”，并且随着反复应激，应激后冻结时间缩短，而WKY大鼠则没有表现出这种习惯现象。这些结果表明了脆弱性。 WKY 大鼠遭受重复应激。虽然急性应激会诱导各个脑区的 c-fos mRNA 表达，但在习惯良好的 Wistar 大鼠中，这些应激诱导的 c-fos mRNA 表达在反复应激后显着降低。应激诱导的 c-fos mRNA 表达在各个脑区同样减少，如下丘脑 (PVN)、隔膜、杏仁核、大脑皮层、蓝斑 (LC) 和中缝核。 Wistar 和 WKY 大鼠迟发反应基因的表达，例如 PVN 中的促肾上腺皮质激素释放激素 (CRH) 基因和 LC 中的酪氨酸羟化酶 (TH) 基因也表现出对重复应激的类似习惯。急性应激增强了 CRH 和 TH 基因的表达，而应激诱导的这些基因的表达随着重复应激后基因表达基础水平的增加而减少。中缝核中 5HTT 基因的表达。 Wistar 和 WKY 大鼠的急性和重复应激均未发生变化，这些结果与 HPA 轴和应激诱导的焦虑行为相反，表明 WKY 大鼠的应激脆弱性。需要检查 WKY 大鼠 PVN 和海马中糖皮质激素受体和加压素基因表达的变化。