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

由于心理-社会压力引起的抑郁，抑郁症患者一直被认为具有应激脆弱性。因此，易应激动物应该是抑郁症的理想模型。与Wistar大鼠相比，Wistar京都(WKY)大鼠对急性应激更敏感、更情绪化，有可能成为抑郁症应激易损性动物模型的候选动物。为了检测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)轴和情绪行为的应激反应。习服良好的Wistar大鼠血浆皮质酮水平在达到峰值后下降，即“增强负反馈”，反复应激后冻结时间缩短，而WKY大鼠则未出现这种习服现象。急性应激诱导不同脑区c-FOS mRNA表达，这些应激诱导c-…的表达反复应激后，习惯性Wistar大鼠脑组织More-FOS基因表达显著降低。WKY大鼠下丘脑腹侧核(PVN)、隔核、杏仁核、大脑皮层、蓝斑(LC)和中缝核等脑区c-fos基因的表达也有相同程度的降低。至于应激诱导的迟发性反应基因的表达，如下丘脑室旁核的促肾上腺皮质激素释放激素(CRH)基因和LC的酪氨酸羟化酶(TH)基因，Wistar和WKY大鼠对重复应激也表现出类似的习惯化。急性应激可促进CRH和TH基因的表达，重复应激后CRH和TH基因的表达随着基础水平的升高而减弱。Wistar和WKY大鼠中缝核内5HTT基因的表达不受急性应激和重复应激的影响。这些结果与HPA轴和应激诱导的焦虑行为的结果相反，表明了WKY大鼠的应激脆弱性。为了阐明这种矛盾的原因，需要检测糖皮质激素受体和加压素基因在WKY大鼠的下丘脑室旁核和海马区的表达变化。较少

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