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

应激易损Fischer 344大鼠作为抑郁症动物模型的可能性研究

• 批准号: 12670942
• 负责人: WATANABE Yoshifumi
• 金额: $ 2.18万
• 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: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670942/
• 关键词: model for depression; Fisher344 rats; stress vulnerability; Hypothalamo - pituitary - adrenal axis; chronic stress; c - fos; antidepressants; periventricular nucleus of hypothalamus; コルチコステロン

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.

本研究的目的是探讨已被证实易受慢性应激影响的 Fischer344 大鼠作为抑郁症合适动物模型的可能性。我们研究了长期服用抗抑郁药丙咪嗪对 Fischer344 大鼠慢性应激适应不良的影响。在这项研究中，我们使用下丘脑-垂体-肾上腺（HPA）轴的应激反应（糖皮质激素（GC）的血药浓度）和c-fos mRNA的表达作为应激适应指标。在不服用抗抑郁药物的情况下，血药浓度模式13天的重复约束应激后，应激过程中GC的变化并没有改变。对于c-fos mRNA表达的应激反应，Fischer344大鼠在重复束缚应激7天后表现出延迟的适应变化，例如应激诱导的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应激3天后就会显现出来。长期给予丙咪嗪可防止Fischer344大鼠HPA轴对重复应激的适应不良，而Fischer344大鼠c-fos mRNA表达适应不良下丘脑室旁核、间隔外侧核和梨状皮层中发现的 ，长期服用并不能纠正丙咪嗪。长期服用丙咪嗪，重复应激7天后，GC血药浓度在应激开始后60分钟急剧下降，应激开始后30分钟峰值浓度没有变化。这些结果表明了预防作用。抗抑郁药对 Fischer344 大鼠应激脆弱性的影响。因此，Fischer344 大鼠可能是具有先天性应激脆弱性的抑郁症的合适动物模型。