Department of Life and Environment Sciences, Section of Neuroscience and Anthropology, University of Cagliari, Cagliari, Italy.
Neuroscience Institute, National Research Council of Italy (CNR), Cagliari, Italy.
Neuropharmacology. 2018 May 1;133:242-253. doi: 10.1016/j.neuropharm.2018.01.045. Epub 2018 Jan 31.
We previously demonstrated that socially isolated rats at weaning showed a significant decrease in corticosterone and adrenocorticotropic hormone (ACTH) levels, associated with an enhanced response to acute stressful stimuli. Here we shown that social isolation decreased levels of total corticosterone and of its carrier corticosteroid-binding globulin, but did not influence the availability of the free active fraction of corticosterone, both under basal conditions and after acute stress exposure. Under basal conditions, social isolation increased the abundance of glucocorticoid receptors, while it decreased that of mineralocorticoid receptors. After acute stress exposure, socially isolated rats showed long-lasting corticosterone, ACTH and corticotrophin releasing hormone responses. Moreover, while in the hippocampus and hypothalamus of group-housed rats glucocorticoid receptors expression increased with time and reached a peak when corticosterone levels returned to basal values, in socially isolated rats expression of glucocorticoid receptors did not change. Finally, social isolation also affected the hypothalamic endocannabinoid system: compared to group-housed rats, basal levels of anandamide and cannabinoid receptor type 1 were increased, while basal levels of 2-arachidonoylglycerol were decreased in socially isolated rats and did not change after acute stress exposure. The present results show that social isolation in male rats alters basal HPA axis activity and impairs glucocorticoid-mediated negative feedback after acute stress. Given that social isolation is considered an animal model of several neuropsychiatric disorders, such as generalized anxiety disorder, depression, post-traumatic stress disorder and schizophrenia, these data could contribute to better understand the alterations in HPA axis activity observed in these disorders.
我们之前曾证明，断奶后被隔离的大鼠皮质酮（corticosterone）和促肾上腺皮质激素（adrenocorticotropic hormone，ACTH）水平显著下降，对急性应激刺激的反应增强。在这里，我们发现社交隔离降低了总皮质酮及其载体皮质类固醇结合球蛋白的水平，但不影响皮质酮游离活性部分的可用性，无论是在基础条件下还是在急性应激暴露后。在基础条件下，社交隔离增加了糖皮质激素受体的丰度，而减少了盐皮质激素受体的丰度。在急性应激暴露后，社交隔离的大鼠表现出持久的皮质酮、ACTH 和促肾上腺皮质激素释放激素反应。此外，在群居大鼠的海马体和下丘脑，糖皮质激素受体的表达随时间增加，并在皮质酮水平恢复到基础值时达到峰值，而在社交隔离的大鼠中，糖皮质激素受体的表达没有变化。最后，社交隔离也影响下丘脑内的内源性大麻素系统：与群居大鼠相比，社交隔离大鼠的基础水平的花生四烯酸酰胺和大麻素受体 1 增加，而基础水平的 2-花生四烯酸甘油减少，且在急性应激暴露后没有变化。本研究结果表明，雄性大鼠的社交隔离改变了基础 HPA 轴活性，并损害了急性应激后的糖皮质激素介导的负反馈。鉴于社交隔离被认为是几种神经精神疾病的动物模型，如广泛性焦虑症、抑郁症、创伤后应激障碍和精神分裂症，这些数据有助于更好地理解这些疾病中 HPA 轴活性的改变。
