Regulation of adenosine A2A receptor gene expression in a model of binge eating in the amygdaloid complex of female rats

  • J Psychopharmacol. 2019 Dec;33(12):1550-1561. doi: 10.1177/0269881119845798.
Maria Vittoria Micioni Di Bonaventura  1 ,  Mariangela Pucci  2 ,  Maria Elena Giusepponi  1 ,  Adele Romano  3 ,  Catia Lambertucci  4 ,  Rosaria Volpini  4 ,  Emanuela Micioni Di Bonaventura  1 ,  Silvana Gaetani  3 ,  Mauro Maccarrone  5  6 ,  Claudio D'Addario  2  7 ,  Carlo Cifani  1
Affiliations
  • 1. School of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, Italy.
  • 2. Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, Italy.
  • 3. Department of Physiology and Pharmacology V. Erspamer, Sapienza University of Rome, Rome, Italy.
  • 4. School of Pharmacy, Medicinal Chemistry Unit, University of Camerino, Camerino, Italy.
  • 5. Campus Bio-Medico, University of Rome, Rome, Italy.
  • 6. European Center for Brain Research (CERC)/Santa Lucia Foundation, Rome, Italy.
  • 7. Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
PMID: 31161847 DOI: 10.1177/0269881119845798
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 (A2AAR) 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 A2AAR promoter region in rats showing binge-like behaviour compared to the control Animals. Focusing thus on A2AAR 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 A2AAR mRNA levels in restricted and stressed rats when compared to the control group. In addition, we observed a significant decrease in A2AAR mRNA levels in rats treated with the A2AAR antagonist (ANR 94) at 1 mg/kg. Consistent changes in the DNA methylation status of the A2AAR promoter were found in restricted and stressed rats after administration of VT 7 or ANR 94.

Conclusion: We confirm the role of A2AAR in binge eating behaviours, and we underline the importance of epigenetic regulation of the A2AAR gene, possibly due to a compensatory mechanism to counteract the effect of binge eating. We suggest that A2AAR activation, inducing receptor gene up-regulation, could be relevant to reduction of food consumption.

Keywords
A2A adenosine receptor; A2A adenosine receptor agonist and antagonist; amygdaloid complex; binge eating; epigenetic regulation; palatable food.
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