Regulation of adenosine A2A receptor gene expression in a model of binge eating in the amygdaloid complex of female rats. (December 2019)

• Record Type: Journal Article
• Authors: Micioni Di Bonaventura, Maria Vittoria; Pucci, Mariangela; Giusepponi, Maria Elena; Romano, Adele; Lambertucci, Catia; Volpini, Rosaria; Micioni Di Bonaventura, Emanuela; Gaetani, Silvana; Maccarrone, Mauro; D'Addario, Claudio; Cifani, Carlo
• Is Part Of: Journal of psychopharmacology. Volume 33:Number 12(2019)
• Page Start: 1550
• Page End: 1561
• Publication Date: 2019-12
• Subjects: A2A adenosine receptor -- A2A adenosine receptor agonist and antagonist -- amygdaloid complex -- binge eating -- epigenetic regulation -- palatable food; Psychopharmacology -- Periodicals; 615.78
• DOI: 10.1177/0269881119845798
• Languages: English
• ISSNs: 0269-8811

Abstract

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 A2A Adenosine Receptor (A2A AR) 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 A2A AR promoter region in rats showing binge-like behaviour compared to the control animals. Focusing thus on A2A AR 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 A2A AR mRNA levels in restricted and stressed rats when compared to the control group. In addition, we observed a significant decrease in A2A AR mRNA levels in rats treated with the A2A AR antagonist (ANR 94) at 1 mg/kg. Consistent changes in the DNA methylation status of the A2A AR promoter were found in restricted and stressed rats after administration of VT 7 or ANR 94. Conclusion: We confirm the role of A2A AR in binge eating behaviours, and we underline the importance of epigenetic regulation of the A2A AR gene, possibly due to a compensatory mechanism to counteract the effect of binge eating. We suggest that A2A AR activation, inducing receptor gene up-regulation, could be relevant to reduction of food consumption.