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，我们研究了产前暴露于轻度应激的动物是否会产生下丘脑-垂体-肾上腺(HPA)轴的过度活动，以及成年后代在应对应激刺激时焦虑或情绪相关行为的变化，以及成年后代单胺类活动的不足，这在抑郁症中是常见的。与对照组相比，在7周龄和28周龄的仔鼠条件恐惧应激期间，产前注射生理盐水应激显著增加皮质酮的分泌。此外，在产前应激组中，观察到在第一次5分钟的高架迷宫中进入张开和闭合手臂的数量减少，这表明产前应激的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，成年子代也观察到了长时间的不动时间，这表明产前应激的子代似乎更容易受到行为‘绝望’的影响。另一方面，与5-羟色胺代谢产物5-羟基吲哚乙酸相比，成年前应激子代的下丘脑中的5-羟色胺浓度高于对照组。这种5-羟色胺能活性的缺陷可能是脆弱因素之一，揭示了HPA轴在对应激刺激的反应中过度活跃。这些应激条件下内分泌反应和行为活动改变的结果以及5-羟色胺能活动的缺陷表明，产前注射生理盐水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.