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。

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670915/
• 关键词: 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

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

由于心理社会压力诱发抑郁，抑郁症患者被认为具有压力易感性。因此，具有应激易感性的动物应该是抑郁症的理想模型。与Wistar大鼠相比，Wistar Kyoto （WKY）大鼠对急性应激敏感且情绪激动，可能是应激易感性抑郁症动物模型的候选者。为了研究WKY大鼠对重复应激的易感性，我们研究了下丘脑-垂体-肾上腺（HPA）轴的应激反应和情绪行为。适应良好的Wistar大鼠在达到峰值后血浆皮质酮水平下降，即“负反馈增强”，反复应激后冻结时间缩短，而WKY大鼠则没有这种适应现象。这些结果表明WKY大鼠对重复应激具有易感性。急性应激诱导不同脑区c-fos mRNA表达，应激诱导的c . More -fos mRNA表达在适应良好的Wistar大鼠反复应激后显著降低。WKY大鼠下丘脑腹侧核（PVN）、中隔、杏仁核、大脑皮层、蓝斑核（LC）和中缝核等脑区c-fos mRNA表达均出现应激性降低。至于应激诱导的晚反应基因表达，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，Wistar和WKY大鼠对重复应激也表现出相似的习惯。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基础表达水平的升高而降低。Wistar和WKY大鼠中缝核5HTT基因的表达在急性和反复应激下均未发生变化。这些结果与HPA轴和应激性焦虑行为的结果相反，表明WKY大鼠存在应激易感性。为了阐明这种矛盾的原因，需要检测WKY大鼠PVN和海马中糖皮质激素受体和抗利尿激素基因表达的变化。少