Ribeirão Preto Medical School, Department of Physiology, University of São Paulo, 14049-900 Ribeirão Preto, SP, Brazil.
Ribeirão Preto Medical School, Department of Physiology, University of São Paulo, 14049-900 Ribeirão Preto, SP, Brazil.
Brain Res. 2019 Nov 15;1723:146402. doi: 10.1016/j.brainres.2019.146402. Epub 2019 Aug 22.
The chronic mild stress (CMS) paradigm is the most frequently investigated animal model for major depression. The hypothalamic-pituitary-adrenal (HPA) axis participates in the generation of depressive symptomatology. We examined whether the depression-like state induced by CMS is associated with immediate changes in HPA axis activation in response to a novel acute stress and whether this response could be modified by hormonal status. Adult female Wistar rats were ovariectomized and received estrogen or vehicle pellets. After 2 weeks, rats were subjected to CMS (or control) conditions for 2.5 or 4.5 weeks. Rats were subsequently subjected to restraint stress for 1 h, and plasma corticosterone (CT) levels were determined before (2:00 p.m.) and after acute stress induction (3:00 and 4:00 p.m.). CT levels and FOS expression were measured in the medial parvocellular subdivision of the PVN (PaMP), central (CeA) and medial amygdala (MeA) and ventral subiculum of the hippocampus (vSub). Plasma CT levels in animals treated with 6.5 weeks of estrogen were elevated before and 1 h after restraint stress induction. Results indicate that the estrogen chronicity and CMS exposure impacted CT secretion. Neuronal PaMP, CeA, MeA and vSub activity decreased after 4.5 weeks of CMS in all groups. No differences were detected between CMS and non-CMS groups. These data suggest that the HPA central hyporesponsiveness observed in the experimental groups subjected to a longer protocol period was independent to CMS paradigm and estrogen treatment restored partially its activity. These data suggest that additional stressors could be responsible for the observed alterations of the HPA axis.
慢性轻度应激（CMS）范式是研究重度抑郁症的最常用动物模型。下丘脑-垂体-肾上腺（HPA）轴参与了抑郁症状的产生。我们研究了 CMS 引起的类似抑郁状态是否与对新的急性应激的 HPA 轴激活的即时变化有关，以及这种反应是否可以通过激素状态来改变。成年雌性 Wistar 大鼠被卵巢切除术，并接受雌激素或载体植入物。2 周后，大鼠接受 CMS（或对照）条件 2.5 或 4.5 周。随后，大鼠进行 1 小时的束缚应激，在急性应激诱导前（下午 2:00）和诱导后（下午 3:00 和 4:00）测定血浆皮质酮（CT）水平。在 PVN 的中多形小细胞亚区（PaMP）、中央（CeA）和内侧杏仁核（MeA）和海马腹侧下托（vSub）中测量 CT 水平和 FOS 表达。接受 6.5 周雌激素治疗的动物的血浆 CT 水平在束缚应激诱导前和 1 小时后升高。结果表明，雌激素的慢性和 CMS 暴露影响 CT 分泌。在所有组中，4.5 周 CMS 后 PaMP、CeA、MeA 和 vSub 的神经元活性降低。CMS 组和非 CMS 组之间没有差异。这些数据表明，在接受较长方案期的实验组中观察到的 HPA 中枢反应性降低与 CMS 范式和雌激素治疗无关，雌激素治疗部分恢复了其活性。这些数据表明，其他应激源可能是 HPA 轴观察到的改变的原因。
