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.