Neuromedin U (NMU) is a highly conserved neuropeptide that has been implicated in the stress response. To better understand how it influences various aspects of the stress response, we studied the effects of intracerebroventricular NMU-8 administration on stress-related behavior and activity of the hypothalamus-pituitary-adrenal (HPA) axis in male C57BL/6J mice. We investigated these NMU-8 effects when mice remained in their home cage and when they were challenged by exposure to forced swim stress. NMU-8 administration resulted in increased grooming behavior in mice that remained in their home cage and in a significant increase in c-Fos immunoreactivity in the paraventricular hypothalamus (PVH) and arcuate nucleus (ARC). Surprisingly, NMU-8 administration significantly decreased plasma corticosterone concentrations. Furthermore, NMU-8 administration increased immobility in the forced swim test in both naïve mice and mice that were previously exposed to swim stress. The effect of NMU-8 on c-Fos immunoreactivity in the PVH was dependent on previous exposure to swim stress given that we observed no significant changes in mice exposed for the first time to swim stress. In contrast, in the ARC we observed a significant increase in c-Fos immunoreactivity regardless of previous stress exposure. Interestingly, NMU-8 administration also significantly decreased plasma corticosterone concentrations in mice that were exposed to single forced swim stress, while this effect was no longer observed when mice were exposed to forced swim stress for a second time. Taken together, our data indicate that NMU-8 regulates stress responsiveness and suggests that its effects depend on previous stress exposure.

中文翻译：

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神经调节素U-8对雄性C57BL / 6J小鼠的应激反应和下丘脑-垂体-肾上腺轴活性的影响。

Neuromedin U（NMU）是一种高度保守的神经肽，与应激反应有关。为了更好地了解它如何影响应激反应的各个方面，我们研究了脑室内NMU-8给药对雄性C57BL / 6J小鼠应激相关行为和下丘脑-垂体-肾上腺（HPA）轴活动的影响。当小鼠留在自己的笼子中以及受到强迫游泳压力的挑战时，我们研究了这些NMU-8的作用。NMU-8给药导致留在其家笼中的小鼠的梳理行为增加，并且在室下丘脑下丘脑（PVH）和弓状核（ARC）中的c-Fos免疫反应性显着提高。出人意料的是，NMU-8给药显着降低了血浆皮质酮浓度。此外，在幼稚的小鼠和先前暴露于游泳压力的小鼠中，在强迫游泳试验中，NMU-8的施用增加了不动性。NMU-8对PVH中c-Fos免疫反应性的影响取决于先前暴露于游泳应激的情况，因为我们观察到首次暴露于游泳应激的小鼠没有明显变化。相反，在ARC中，我们观察到c-Fos免疫反应性显着增加，而与先前的压力暴露无关。有趣的是，NMU-8的施用还显着降低了暴露于单次强迫游泳压力的小鼠的血浆皮质酮浓度，而当小鼠第二次暴露于强迫游泳的压力时，则不再观察到这种效果。在一起