Stress and obesity are highly prevalent conditions, and the mechanisms through which stress affects food intake are complex. In the present study, stress-induced activation in neuropeptide systems controlling ingestive behavior was determined. Adult male rats were exposed to acute (30 min/d × 1 d) or repeated (30 min/d × 14 d) restraint stress, followed by transcardial perfusion 2h after the termination of the stress exposure. Brain tissues were harvested, and 30 µm sections through the hypothalamus were immunohistochemically stained for Fos protein, which was then co-localized within neurons staining positively for the type 4 melanocortin receptor (MC4R), the glucagon-like peptide-1 receptor (GLP1R), or agouti-related peptide (AgRP). Cell counts were performed in the paraventricular (PVH), arcuate (ARC) and ventromedial (VMH) hypothalamic nuclei and in the lateral hypothalamic area (LHA). Fos was significantly increased in all regions except the VMH in acutely stressed rats, and habituated with repeated stress exposure, consistent with previous studies. In the ARC, repeated stress reduced MC4R cell activation while acute restraint decreased activation in GLP1R neurons. Both patterns of stress exposure reduced the number of AgRP-expressing cells that also expressed Fos in the ARC. Acute stress decreased Fos-GLP1R expression in the LHA, while repeated restraint increased the number of Fos-AgRP neurons in this region. The overall profile of orexigenic signaling in the brain is thus enhanced by acute and repeated restraint stress, with repeated stress leading to further increases in signaling, in a region-specific manner. Stress-induced modifications to feeding behavior appear to depend on both the duration of stress exposure and regional activation in the brain. These results suggest that food intake may be increased as a consequence of stress, and may play a role in obesity and other stress-associated metabolic disorders.

Hypertension is a risk factor for stroke, and has been correlated with HPA axis sensitization and the initiation of immune/inflammatory processes during chronic stress. Our study examined whether hypertension affects the stress‐induced activation of brain regions involved in the generation of stress responses and cardiovascular control. Spontaneously hypertensive (SHR) and normotensive Wistar‐Kyoto (WKY) male rats were acutely (30min x 1d) or repeatedly (30min x 14d) restrained or were not stressed. Perfused brain sections were immunohistochemically stained for Fos, which was quantified in the paraventricular (PVH) and dorsomedial (DMH) nuclei and the central (CeA) and medial (MeA) amygdala. Acute stress increased Fos in the PVH and DMH of WKY rats, compared to controls, and this response habituated with repeated stress exposure. Similar results were seen in control and acute SHRs, but the habituation of Fos induction was not seen in the PVH and only partially occurred in the DMH of these animals after repeated stress. MeA and CeA responses varied by stress treatment but were largely similar in the two strains. The data suggest that hypertension leads to enhanced responses to chronic stress at the level of neuronal activation. Understanding stress‐hypertension interactions in the central nervous system will aid the development of treatments for these and related conditions. Support: NIH 5G12 RR008124