Repeated binge‐like eating episodes in female rats alter adenosine A2A and dopamine D2 receptor genes regulation in the brain reward system

Abstract Objective Binge‐eating disorder is an eating disorder characterized by recurrent binge‐eating episodes, during which individuals consume excessive amounts of highly palatable food (HPF) in a short time. This study investigates the intricate relationship between repeated binge‐eating episode and the transcriptional regulation of two key genes, adenosine A 2A receptor ( A 2A AR ) and dopamine D2 receptor ( D2R ), in selected brain regions of rats. Method Binge‐like eating behavior on HPF was induced through the combination of food restrictions and frustration stress (15 min exposure to HPF without access to it) in female rats, compared to control rats subjected to only restriction or only stress or none of these two conditions. After chronic binge‐eating episodes, nucleic acids were extracted from different brain regions, and gene expression levels were assessed through real‐time quantitative PCR. The methylation pattern on genes' promoters was investigated using pyrosequencing. Results The analysis revealed A 2A AR upregulation in the amygdala and in the ventral tegmental area (VTA), and D2R downregulation in the nucleus accumbens in binge‐eating rats. Concurrently, site‐specific DNA methylation alterations at gene promoters were identified in the VTA for A 2A AR and in the amygdala and caudate putamen for D2R . Discussion The alterations on A 2A AR and D2R genes regulation highlight the significance of epigenetic mechanisms in the etiology of binge‐eating behavior, and underscore the potential for targeted therapeutic interventions, to prevent the development of this maladaptive feeding behavior. These findings provide valuable insights for future research in the field of eating disorders. Public Significance Using an animal model with face, construct, and predictive validity, in which cycles of food restriction and frustration stress evoke binge‐eating behavior, we highlight the significance of epigenetic mechanisms on adenosine A 2A receptor ( A 2A AR ) and dopamine D2 receptor ( D2R ) genes regulation. They could represent new potential targets for the pharmacological management of eating disorders characterized by this maladaptive feeding behavior.