Laboratory of Behavioral Genetics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Laboratory of Behavioral Genetics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Psychoneuroendocrinology. 2019 Mar;101:101-110. doi: 10.1016/j.psyneuen.2018.11.003. Epub 2018 Nov 3.
The two stress-responsive physiological systems, autonomic nervous system (ANS) and hypothalamus-pituitary-adrenal (HPA) axis exert complementary and interrelated actions in the organism. Individuals that suffer stress-related psychopathologies frequently present simultaneous alterations -i.e., either low or high- responsiveness- in both systems. However, there is scarce evidence establishing whether a priori alterations in these systems -i.e., independent of previous stress exposure- may predispose to the development of psychopathologies possibly due to the lack of animal models simultaneously involving aberrant HPA and SNS responses. In this study, we describe two animal models selectively bred according to their differential (either high, 'High', or low, 'Low') glucocorticoid responsiveness to stress, in comparison to a third line of rats that displays intermediate ('Inter') glucocorticoid responses. The two extreme lines may be considered distinct models of psychopathology; the High line representing a model of constitutive mood alterations while the Low line a model of vulnerability to develop stress-induced psychopathologies. We recorded the electrocardiogram in rats from the three lines and quantified heart rate variability and vagal tone indexes during rest and stress challenges. Rats from both High and Low lines displayed higher heart rate and lower basal vagal tone than the Inter group, both at resting and following stress exposure. Specific pharmacological manipulations probing the relative contribution of sympathetic and parasympathetic components on HR modulation confirmed a relative lower vagal tone in High and Low lines and discarded differences in the sympathetic regulation of heart rate between the lines. Therefore, the two genetically-selected High and Low glucocorticoid rat lines emerge as two valuable preclinical models of psychopathology involving two key risk factors for psychiatric and cardiovascular disorders, namely dysregulations in the HPA axis and cardiac vagal functioning.
两个应激反应生理系统，自主神经系统（ANS）和下丘脑-垂体-肾上腺（HPA）轴，在生物体中发挥互补和相互关联的作用。患有与应激相关的精神病理学的个体通常同时存在两种系统的改变——即低或高反应性。然而，几乎没有证据表明这些系统的预先改变——即独立于先前的应激暴露——可能导致精神病理学的发展，这可能是由于缺乏同时涉及 HPA 和 SNS 反应异常的动物模型。在这项研究中，我们描述了两种根据其对应激的糖皮质激素反应的差异（高，“高”或低，“低”）选择性繁殖的动物模型，与显示中间（“中”）糖皮质激素反应的第三组大鼠进行比较。这两个极端的线可能被认为是不同的精神病理学模型；高线代表了一种与情绪改变有关的模型，而低线则代表了一种易患应激诱导的精神病理学的模型。我们记录了来自这三个系的大鼠的心电图，并在休息和应激挑战期间量化了心率变异性和迷走神经张力指数。高线和低线的大鼠在休息和应激暴露后，心率均高于中线，基础迷走神经张力也较低。探测交感和副交感成分对 HR 调节相对贡献的特定药理学操作证实，高线和低线的迷走神经张力较低，并排除了对线之间心率的交感调节的差异。因此，两种基因选择的高和低糖皮质激素大鼠系作为涉及 HPA 轴和心脏迷走神经功能障碍两个关键风险因素的精神病理学的两个有价值的临床前模型出现。
