Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Psychoneuroendocrinology. 2012 Aug;37(8):1209-23. doi: 10.1016/j.psyneuen.2011.12.014. Epub 2012 Jan 11.
Emerging evidence indicates that certain behavioral traits, such as anxiety, are associated with the development of depression-like behaviors after exposure to chronic stress. However, single traits do not explain the wide variability in vulnerability to stress observed in outbred populations. We hypothesized that a combination of behavioral traits might provide a better characterization of an individual's vulnerability to prolonged stress. Here, we sought to determine whether the characterization of relevant behavioral traits in rats could aid in identifying individuals with different vulnerabilities to developing stress-induced depression-like behavioral alterations. We also investigated whether behavioral traits would be related to the development of alterations in the hypothalamic-pituitary-adrenal axis and in brain activity - as measured through phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2)--in response to an acute stressor following either sub-chronic (2 weeks) or chronic (4 weeks) unpredictable stress (CUS). Sprague-Dawley rats were characterized using a battery of behavioral tasks, and three principal traits were identified: anxiety, exploration and activity. When combined, the first two traits were found to explain the variability in the stress responses. Our findings confirm the increased risk of animals with high anxiety developing certain depression-like behaviors (e.g., increased floating time in the forced swim test) when progressively exposed to stress. In contrast, the behavioral profile based on combined low anxiety and low exploration was resistant to alterations related to social behaviors, while the high anxiety and low exploration profile displayed a particularly vulnerable pattern of physiological and neurobiological responses after sub-chronic stress exposure. Our findings indicate important differences in animals' vulnerability and/or resilience to the effects of repeated stress, particularly during initial or intermediate levels of stress exposure, and they highlight that the behavioral inhibition profile of an animal provides a particular susceptibility to responding in a deleterious manner to stress.
新出现的证据表明，某些行为特征，如焦虑，与慢性应激后出现的抑郁样行为发展有关。然而，单一特征并不能解释在广泛的应激易感性中观察到的变异性。我们假设，行为特征的组合可能更好地描述个体对长期应激的易感性。在这里，我们试图确定大鼠相关行为特征的表征是否有助于识别对发展应激诱导的抑郁样行为改变具有不同易感性的个体。我们还研究了行为特征是否与下丘脑-垂体-肾上腺轴和大脑活动的改变有关，这些改变是通过细胞外信号调节激酶 1/2（ERK1/2）的磷酸化来衡量的，以应对亚慢性（2 周）或慢性（4 周）不可预测应激（CUS）后的急性应激源。使用一系列行为任务对 Sprague-Dawley 大鼠进行特征描述，确定了三个主要特征：焦虑、探索和活动。当结合使用时，前两个特征被发现可以解释应激反应的可变性。我们的研究结果证实，具有高焦虑的动物在逐渐暴露于应激时，有发展出某些抑郁样行为（例如，强迫游泳试验中漂浮时间增加）的高风险。相比之下，基于低焦虑和低探索的行为特征对与社会行为相关的改变具有抵抗力，而高焦虑和低探索特征在亚慢性应激暴露后表现出特别脆弱的生理和神经生物学反应模式。我们的研究结果表明，动物对重复应激的易感性和/或弹性存在重要差异，特别是在应激暴露的初始或中间阶段，并且它们突出表明动物的行为抑制特征特别容易以有害的方式对压力做出反应。
