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慢性轻度应激在高焦虑雌性 Long Evans 大鼠中诱导出不同的抑郁样症状和 c-Fos 及 5HT1A 蛋白水平。

Chronic mild stress induces differential depression-like symptoms and c-Fos and 5HT1A protein levels in high-anxiety female Long Evans rats.

机构信息

Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA.

Developmental and Brain Sciences Program, Department of Psychology, University of Massachusetts Boston, Boston, MA, USA.

出版信息

Behav Brain Res. 2023 Feb 13;438:114202. doi: 10.1016/j.bbr.2022.114202. Epub 2022 Nov 4.

Abstract

Depression and anxiety disorders overlap in clinical populations, suggesting common mechanisms that may be further investigated in reliable animal models. We used filial 8 female Long-Evans rats bred for high (HAn; n = 19) and low anxiety (LAn)-like behavior (n = 21) to assess forced swim test mobility strategies and chronic mild stress (CMS)-induced depression-like symptoms. We measured (1) weight, (2) fur piloerection, (3) sweet food consumption, (4) grooming behavior, and (5) circulating estradiol (E2). One month after CMS terminated and following a terminal forced swim test, brains were processed for immunohistochemistry targeting c-Fos and serotonin 1 A receptor (5-HT1AR) protein in the paraventricular nucleus (PVN) of the hypothalamus. HAn female rats showed increased anxiety-like behavior (i.e., lower open to closed arm ratios, increased closed arm entries), more swimming (i.e., mobility), and less floating (i.e., immobility) behavior in the forced swim test. Overall, HAn females weighed less than their LAn counterparts. After chronic mild stress, HAn lines displayed even greater mobility and consumed fewer Froot Loops™. Fur and grooming analyses indicated no significant differences in mean counts across experimental groups. One month after CMS, cycling E2 concentrations (pg/ml) did not differ between HAn and LAn animals. Elevated c-Fos and 5-HT1AR expression were observed in the PVN, where HAn CMS rats expressed the most c-Fos and 5-HT1AR immunoreactivity. In summary, outbred HAn rats show robust anxiety-like behavior, exhibit more mobility in the forced swim test, and are more sensitive to chronic mild stress-induced grooming and decline in palatable food ingestion.

摘要

抑郁和焦虑障碍在临床人群中存在重叠,这表明可能在可靠的动物模型中进一步研究共同的机制。我们使用繁殖的第 8 代雌性长耳大仓鼠(Long-Evans rats),这些仓鼠繁殖为高(HAn;n=19)和低焦虑(LAn)样行为(n=21),以评估强迫游泳测试的移动策略和慢性轻度应激(CMS)诱导的抑郁样症状。我们测量了(1)体重、(2)皮毛竖立、(3)甜食消耗、(4)梳理行为和(5)循环雌二醇(E2)。在 CMS 结束一个月后,并在最后一次强迫游泳测试后,我们处理了大脑,用于下丘脑室旁核(PVN)中 c-Fos 和 5-羟色胺 1A 受体(5-HT1AR)蛋白的免疫组织化学靶向。HAn 雌性大鼠表现出更高的焦虑样行为(即,较低的开放臂与封闭臂比率,增加的封闭臂进入次数),在强迫游泳测试中表现出更多的游泳(即,移动)和更少的漂浮(即,不动)行为。总体而言,HAn 雌性大鼠的体重低于 LAn 对照。在慢性轻度应激后,HAn 品系显示出更大的流动性,并且消耗的 Froot Loops™更少。皮毛和梳理分析表明,实验组之间的平均计数没有显着差异。在 CMS 一个月后,HAn 和 LAn 动物之间的循环 E2 浓度(pg/ml)没有差异。在 PVN 中观察到 c-Fos 和 5-HT1AR 表达增加,其中 HAn CMS 大鼠表达最多的 c-Fos 和 5-HT1AR 免疫反应性。总之,远交 HAn 大鼠表现出强烈的焦虑样行为,在强迫游泳测试中表现出更多的移动性,并且对慢性轻度应激诱导的梳理和美味食物摄入减少更为敏感。

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