Walker Sophie E, Zanoletti Olivia, Guillot de Suduiraut Isabelle, Sandi Carmen
Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland.
Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland.
Psychoneuroendocrinology. 2017 Oct;84:1-10. doi: 10.1016/j.psyneuen.2017.06.011. Epub 2017 Jun 16.
Glucocorticoids coordinate responses that enable an individual to cope with stressful challenges and, additionally, mediate adaptation following cessation of a stressor. There are important individual differences in the magnitude of glucocorticoid responsiveness to stressors. However, whether individual differences in glucocorticoid responsiveness to stress are linked to different behavioral strategies in coping with social and non-social challenges is not easily studied, owing to the lack of appropriate animal models. To address this, we generated three lines of Wistar rats selectively bred for the magnitude of their glucocorticoid responses following exposure to a variety of stressors over three consecutive days at juvenility. Here, we present findings following observations of a high level of variation in glucocorticoid responsiveness to stress in outbred Wistar rats, and the strong response to selection for this trait over a few generations. When challenged with different stressful challenges, rats from the three lines differed in their coping behaviors. Strikingly, the line with high glucocorticoid responsiveness to stress displayed enhanced aggression and anxiety-like behaviors. In addition, these rats also showed alterations in the expression of genes within both central and peripheral nodes of the hypothalamic-pituitary-adrenal (HPA) axis and enhanced reactivity to acute stress exposure. Together, these findings strongly link differences in glucocorticoid responsiveness to stress with marked differences in coping styles. The developed rat lines are thus a promising model with which to examine the relationship between variation in reactivity of the HPA axis and stress-related pathophysiology and could be employed to assess the therapeutic potential of treatments modulating stress habituation to ameliorate psychopathology.
糖皮质激素协调各种反应，使个体能够应对压力挑战，此外，还介导应激源停止后的适应过程。糖皮质激素对应激源的反应程度存在重要的个体差异。然而，由于缺乏合适的动物模型，糖皮质激素对应激反应的个体差异是否与应对社会和非社会挑战的不同行为策略相关，并不容易研究。为了解决这个问题，我们培育了三系Wistar大鼠，这些大鼠在幼年时连续三天暴露于各种应激源后，根据其糖皮质激素反应的程度进行选择性繁殖。在此，我们展示了对远交Wistar大鼠糖皮质激素对应激反应高度变异的观察结果，以及几代人对该性状选择的强烈反应。当面对不同的压力挑战时，这三系大鼠的应对行为存在差异。引人注目的是，糖皮质激素对应激反应高的品系表现出增强的攻击性和类似焦虑的行为。此外，这些大鼠在下丘脑 - 垂体 - 肾上腺（HPA）轴的中枢和外周节点内的基因表达也发生了改变，并且对急性应激暴露的反应性增强。总之，这些发现有力地将糖皮质激素对应激反应的差异与应对方式的显著差异联系起来。因此，所培育的大鼠品系是一个很有前景的模型，可用于研究HPA轴反应性变化与应激相关病理生理学之间的关系，并可用于评估调节应激习惯化以改善精神病理学的治疗潜力。
