Regulation of adenosine A_2A receptor gene expression in a model of binge eating in the amygdaloid complex of female rats

Background: Pharmacological treatment approaches for eating disorders, such as binge eating disorder and bulimia nervosa, are currently limited. Methods and aims: Using a well-characterized animal model of binge eating, we investigated the epigenetic regulation of the A_2A Adenosine Receptor (A_2AAR) and dopaminergic D2 receptor (D2R) genes. Results: Gene expression analysis revealed a selective increase of both receptor mRNAs in the amygdaloid complex of stressed and restricted rats, which exhibited binge-like eating, when compared to non-stressed and non-restricted rats. Consistently, pyrosequencing analysis revealed a significant reduction of the percentage of DNA methylation but only at the A_2AAR promoter region in rats showing binge-like behaviour compared to the control animals. Focusing thus on A_2AAR agonist (VT 7) administration (which inhibited the episode of binge systemically at 0.1 mg/kg or intra-central amygdala (CeA) injection at 900 ng/side) induced a significant increase of A_2AAR mRNA levels in restricted and stressed rats when compared to the control group. In addition, we observed a significant decrease in A_2AAR mRNA levels in rats treated with the A_2AAR antagonist (ANR 94) at 1 mg/kg. Consistent changes in the DNA methylation status of the A_2AAR promoter were found in restricted and stressed rats after administration of VT 7 or ANR 94. Conclusion: We confirm the role of A_2AAR in binge eating behaviours, and we underline the importance of epigenetic regulation of the A_2AAR gene, possibly due to a compensatory mechanism to counteract the effect of binge eating. We suggest that A_2AAR activation, inducing receptor gene up-regulation, could be relevant to reduction of food consumption.