Study on the possibility of the Fischer 344 rats with stress-vulnerability for an animal model for depression

这项研究的目的是调查fisher 344老鼠的可能性，这些老鼠已经被证实易受慢性压力的影响，作为合适的抑郁症动物模型。我们研究了长期服用抗抑郁药丙咪嗪对fisher 344大鼠慢性应激适应不良的影响。在本研究中，我们将下丘脑-垂体-肾上腺（HPA）轴的应激反应（血糖皮质激素（GC）浓度）和c-fos mRNA的表达作为应激适应的指标。在不服用抗抑郁药的情况下，应激过程中GC血药浓度变化规律在13 d内无明显变化。在c-fos mRNA表达的应激反应方面，fisher 344大鼠在重复约束应激7天后表现出延迟的适应性变化，如应激诱导的c-fos mRNA表达增加减少。通常，c-fos mRNA的这种适应性变化在正常适应条件下应激3天后才会显现出来。长期给药丙帕明可防止fisher 344大鼠HPA轴对反复应激的不适应，而下丘脑室旁核、中隔外侧核和梨状皮质中c-fos mRNA表达的不适应，长期给药丙帕明不能纠正。长期给药丙咪嗪后，经7 d反复应激，应激开始后60 min血GC浓度显著下降，应激开始后30 min血GC浓度峰值无变化。提示抗抑郁药对Fischer344大鼠应激易感性的预防作用。因此，fisher 344大鼠可能是先天性应激易感性抑郁症的合适动物模型。

The aim of this study is to investigate the possibility of the Fischer344 rats, who have been confirmed to be vulnerable to chronic stress, for a suitable animal model for depression. We investigated the effects of long-term administration of an antidepressant, imipramine, on maladaptation of Fischer344 rats to chronic stress. In this study, we used stress-responses of Hypothalamo-pituitary-adrenal (HPA) axis (blood concentration of glucocorticoids (GC)) and expression of c-fos mRNA as indices of stress adaptation.Without antidepressant administration, the pattern of blood concentration alteration of GC during stress was not changed with repeated restraint stress for 13 days. As for stress response of c-fos mRNA expression, Fischer344 rats showed delayed adapted change, such as a reduction of stress-induced increase in expression of c-fos mRNA, after repeated restraint stress for seven days. Usually, this adapted change of c-fos mRNA is revealed after three days stress in normal adaptation.Long-term administration of imipramine prevented the HPA axis of Fischer344 rats from maladaptaion to repeated stress, while maladaptation of c-fos mRNA expression of Fischer344 rats, which was revealed in paraventricular nucleus of hypothalamus, lateral nucleus of septum, and piriform cortex, was not corrected by long-term administration of imipramine. With long-term administration of imipramine, blood concentration of GC was decreased dramatically 60 min after the beginning of stress after seven days repeated stress, without an alteration of peak concentration at 30 min after the beginning of stress.These results suggest the preventive effect of antidepressants on stress vulnerability of Fischer344 rats. Consequently, it is plausible that Fischer344 rats could be a suitable animal model for depression with congenital stress vulnerability.