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

由于心理社会压力诱导抑郁症，抑郁症患者被认为具有压力脆弱性。那是压力脆弱性的动物应该是抑郁症的理想模型。与Wistar大鼠相比，对急性压力敏感且情绪激动的Wistar Kyoto（WKY）大鼠可能是抑郁症模型的候选抑郁模型，并具有压力脆弱性，我们研究了WKY大鼠对重复压力的脆弱性，我们研究了假设垂体 - 垂体 - 肾上腺肾上腺轴（HPA）轴心的压力反应和情感上的情感行为。养护良好的Wistar大鼠在达到峰值水平后表现出血浆皮质酮水平的降低，即“负反反馈的增强”，并且在压力重复应激后冻结时间缩短，而WKY大鼠没有显示出这种习惯现象。这些结果表明WKY大鼠反复应激的脆弱性。尽管急性应激诱发了各个大脑区域的C-FOS mRNA表达，但这些应激诱导的C…更多的FOS mRNA表达在良好的Wistar大鼠中反复应激后大大降低。 WKY大鼠在各种大脑区域（例如下丘脑周围核核（PVN），Septum，Septum，Amygdala，Cerebral Cortex，coreerbral Cortex，locus coreruleus（LC）和Raphe Nucucus中，WKY大鼠表现出应力诱导的C-FOS mRNA表达的降低。至于应激诱导的晚期反应基因的表达，例如在LC中PVN和酪氨酸羟化酶（Th）基因中释放的马酮（CRH）基因，Wistar和Wky大鼠都表现出与重复应力相似的习惯。急性应激增强了CRH和TH基因表达的表达，而在重复应激后，应力诱导的这些基因的表达降低了基因表达的基本水平。 Wistar和WKY大鼠的急性和重复应力不会改变5HTT基因在Raphe核中的表达。这些结果与HPA轴和压力引起的焦虑行为的结果相反，后者表明WKY大鼠的压力脆弱性。为了阐明这种矛盾的原因，需要检查糖皮质激素受体和加压素在PVN和WKY大鼠的海马中的基因表达的改变。