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

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

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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