Epigenetic regulation of nociceptin/orphanin FQ and corticotropin-releasing factor system genes in frustration stress-induced binge-like palatable food consumption

Evidence suggests that binge eating may be caused by a unique interaction between dieting and stress. We developed a binge‐eating model in which female rats with a history of intermittent food restriction show binge‐like palatable food consumption after a 15‐minute exposure to the sight of the palatable food (frustration stress). The aim of the present study was to investigate the regulation of the stress neurohormone corticotropin‐releasing factor (CRF) system and of the nociceptin/orphanin FQ (N/OFQ) system genes in selective rat brain regions, using our animal model. Food restriction by itself seems to be responsible in the hypothalamus for the downregulation on messenger RNA levels of CRF‐1 receptor, N/OFQ and its receptor (NOP). For the latter, this alteration might be due to selective histone modification changes. Instead, CRF gene appears to be upregulated in the hypothalamus as well as in the ventral tegmental area only when rats are food restricted and exposed to frustration stress, and, of relevance, these changes appear to be due to a reduction in DNA methylation at gene promoters. Moreover, also CRF‐1 receptor gene resulted to be differentially regulated in these two brain regions. Epigenetic changes may be viewed as adaptive mechanisms to environmental perturbations concurring to facilitate food consumption in adverse conditions, that is, in this study, under food restriction and stressful conditions. Our data on N/OFQ and CRF signaling provide insight on the use of this binge‐eating model for the study of epigenetic modifications in controlled genetic and environmental backgrounds. Binge eating is triggered by a unique interaction between dieting and stress. We observed that rats subjected to cycles of food restriction and then exposed to frustration stress showed binge eating. We provide data on target gene expression regulation (CRF and N/OFQ system genes) via epigenetic mechanisms, suggesting differential roles in selected brain regions. In the VTA, CRF system gene upregulation in response to stress might lead to the increase of high palatable food consumption through modulation of reward mechanisms.