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

Francesca Mercante; Emanuela Micioni Di Bonaventura; Mariangela Pucci; Luca Botticelli; Carlo Cifani; Claudio D'Addario; Maria Vittoria Micioni Di Bonaventura

doi:10.1002/eat.24216

Repeated binge-like eating episodes in female rats alter adenosine A_2A and dopamine D2 receptor genes regulation in the brain reward system

Int J Eat Disord. 2024 Apr 23. doi: 10.1002/eat.24216. Online ahead of print.

Authors

Francesca Mercante¹, Emanuela Micioni Di Bonaventura², Mariangela Pucci^{1

3}, Luca Botticelli², Carlo Cifani², Claudio D'Addario^{1

4}, Maria Vittoria Micioni Di Bonaventura²

Affiliations

¹ Department of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, Italy.
² Pharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy.
³ Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden.
⁴ Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

PMID: 38650547
DOI: 10.1002/eat.24216

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_2AAR) 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_2AAR 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_2AAR and in the amygdala and caudate putamen for D2R.

Discussion: The alterations on A_2AAR 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_2AAR) 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.

Keywords: adenosine A2A receptor (A2AAR); animal model; binge eating; brain reward system; dopamine D2 receptor (D2R); epigenetics; female rats; rat's brain.

Abstract

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