Strategies for the study of the disinhibition of Hypothalamic-Pituitary-Adrenal axis in affective disorders, using prenatal stress model.

在这项研究中，我们调查了动物在产前暴露于轻度压力下是否会产生下丘脑-垂体-肾上腺（HPA）轴的过度活动，以及对压力刺激的焦虑或情绪相关行为的改变，以及成年后代单胺能活动的缺陷，这在抑郁症中很常见。与对照组相比，产前生理盐水注射应激显著增加了条件恐惧应激条件下7周龄和28周龄子代皮质酮的分泌。此外，在前5分钟的高架加迷宫中，应激组进入张开和闭合双臂的次数减少，这表明在新的环境条件下，应激组的后代比对照组更焦虑。在强迫游泳测试中，在产前应激的成年后代中也观察到长时间的不动时间，这表明产前应激的后代似乎容易产生行为“绝望”。另一方面，与未改变的血清素代谢物5-羟基吲哚乙酸相比，产前应激后代成年后下丘脑中的5-羟色胺浓度高于对照组。这种血清素活性的缺失可能是易感因素之一，揭示了HPA轴在应激刺激反应中的过度活动。应激条件下的内分泌反应和行为活动的改变以及血清素能活性的缺失表明，产前生理盐水注射应激模型作为抑郁症的动物模型可能具有表面有效性。

In this study we have investigated whether animals prenatally exposed to mild stress produce the overactivity of Hypothalamo-Pituitary-Adrenal (HPA) axis and alterations of anxiety-or mood-related behaviors in the response to stressful stimuli as well as a deficit of monoaminergic activities in adult offspring, which are frequently seen in depression. The prenatal saline injection stress increased the corticosterone secretion to a significantly greater extent during conditioned fear stress in offspring at 7 and 28 weeks of age in comparison with controls. In addition, decreased entry numbers into open and closed arms in elevated plus maze for the first 5-min session were observed in the prenatally stressed groups, suggesting that prenatally stressed offspring were more anxious under the new environmental conditions than controls. A prolonged immobility duration in forced swimming test was also observed in the prenatally stressed adult offspring, indicating that the prenatally stressed offspring seemed to be susceptible to behavioral'despair'. On the other hand, the 5-hydroxytryptamine concentration in the hypothalamus from prenatally stressed offspring in adulthood was observed to be higher than controls, in contrast of unaltered serotonin metabolite, 5-hydroxyindoleacetic acid. This deficit of serotonergic activity may be one of the vulnerability factors, revealing overactivity of the HPA axis in the response to stressful stimuli. These results of endocrine response and altered behavioral activity under stressful conditions, and the deficit of serotonergic activity suggest that the prenatal saline injection stress model may have a face validity as an animal model of depression.