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两种抑郁症基因动物模型中的应激激素与情绪调节

Stress hormones and emotion-regulation in two genetic animal models of depression.

作者信息

Braw Y, Malkesman O, Merlender A, Bercovich A, Dagan M, Maayan R, Weizman A, Weller A

机构信息

Department of Psychology, and the Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan 52900, Israel.

出版信息

Psychoneuroendocrinology. 2006 Oct;31(9):1105-16. doi: 10.1016/j.psyneuen.2006.07.003. Epub 2006 Sep 18.

Abstract

Children of depressed parents often exhibit emotion-regulation deficits, characterized by either excessive withdrawal or approach strategies toward the mother. The current study examined behavioral and physiological emotion-regulation in preweanling pups (postnatal day 17-19) belonging to two different genetic animal models of depression, Wistar-Kyoto (WKY) and Flinders Sensitive-Line (FSL) rats. The study also examined the effects of stress on the two animal models, hypothesizing an interactive effect of hereditary vulnerability and exposure to stress. Chronic-stress was simulated by providing limited bedding to the dam and litter for a week, in the early postnatal period. Acute-stress was generated by exposure to an adult male rat, an ethologically valid stressor. Emotion-regulation of the pups was examined using a Y-maze preference test and radioimmunoassay of Hypothalamic-Pituitary-Adrenal (HPA) axis hormones (corticosterone & adreno-corticotropin/ACTH). WKY and FSL pups exhibited reduced approach-behavior toward the dam, an emotion-regulation profile reminiscent of avoidant attachment evident in many children of depressed parents. In contrast, the two animal models did not show similar HPA axis activity. FSL pups exhibited markedly lower ACTH levels compared to controls, while WKY pups did not differ from controls. With regard to the stress manipulations, the limited-bedding condition had no effect, while the acute-stressor induced overall effects on all groups, with more pronounced reactivity evident in the WKY and FSL pups. Taken together, the experiments indicate a similar behavioral profile of the two strains at the preweanling period, while suggesting HPA dysfunction in only one of the strains.

摘要

父母患有抑郁症的孩子往往表现出情绪调节缺陷,其特征是对母亲要么过度退缩,要么采取亲近策略。当前的研究考察了断奶前幼崽(出生后第17 - 19天)的行为和生理情绪调节,这些幼崽来自两种不同的抑郁症基因动物模型,即Wistar - Kyoto(WKY)大鼠和弗林德斯敏感系(FSL)大鼠。该研究还考察了应激对这两种动物模型的影响,假设遗传易感性和应激暴露之间存在交互作用。在出生后早期,通过给母鼠和幼崽提供有限的垫料来模拟慢性应激,为期一周。通过让幼崽接触成年雄性大鼠来产生急性应激,这是一种符合行为学的有效应激源。使用Y迷宫偏好测试和下丘脑 - 垂体 - 肾上腺(HPA)轴激素(皮质酮和促肾上腺皮质激素/ACTH)的放射免疫测定法来检测幼崽的情绪调节。WKY和FSL幼崽对母鼠的亲近行为减少,这种情绪调节特征让人联想到许多父母患有抑郁症的孩子所表现出的回避型依恋。相比之下,这两种动物模型并未表现出相似的HPA轴活性。与对照组相比,FSL幼崽的ACTH水平明显较低,而WKY幼崽与对照组没有差异。关于应激操作,有限垫料条件没有影响,而急性应激源对所有组都产生了总体影响,WKY和FSL幼崽的反应性更明显。综上所述,实验表明这两个品系在断奶前期具有相似的行为特征,同时表明只有其中一个品系存在HPA功能障碍。

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