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，我们已经调查了动物产前暴露于轻度应激是否产生过度活跃的下丘脑-垂体-肾上腺（HPA）轴和改变焦虑或情绪相关的行为在应激刺激的反应，以及赤字的单胺能活动在成年后代，这是常见的抑郁症。产前生理盐水注射压力增加皮质酮分泌到一个显着更大的程度上在条件性恐惧压力的后代在7和28周龄与对照组相比。此外，在产前应激组中观察到前5分钟高架十字迷宫中开放臂和闭合臂的进入次数减少，表明产前应激后代在新的环境条件下比对照组更焦虑。在强迫游泳试验中，产前应激的成年子代也观察到了延长的不动时间，表明产前应激的子代似乎更容易出现行为“绝望”。另一方面，5-羟色胺浓度在下丘脑从产前强调后代在成年期被观察到高于对照组，在未改变的5-羟色胺代谢产物，5-羟吲哚乙酸的对比。这种多巴胺能活动的缺陷可能是脆弱性因素之一，揭示了HPA轴在应激刺激反应中的过度活动。这些结果的内分泌反应和改变的行为活动在压力条件下，和赤字的肾上腺素能活动表明，产前生理盐水注射应激模型可能有一个表面效度作为抑郁症的动物模型。

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.