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.

Regulation of adenosine A2A receptor gene expression in a model of binge eating in the amygdaloid complex of female rats / Micioni Di Bonaventura, M. V.; Pucci, M.; Giusepponi, M. E.; Romano, A.; Lambertucci, C.; Volpini, R.; Micioni Di Bonaventura, E.; Gaetani, S.; Maccarrone, M.; D'Addario, C.; Cifani, C.. - In: JOURNAL OF PSYCHOPHARMACOLOGY. - ISSN 0269-8811. - 33:12(2019), pp. 1550-1561. [10.1177/0269881119845798]

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

Romano A.;Gaetani S.;
2019

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.
2019
A; 2A; adenosine receptor; A; 2A; adenosine receptor agonist and antagonist; amygdaloid complex; binge eating; epigenetic regulation; palatable food
01 Pubblicazione su rivista::01a Articolo in rivista
Regulation of adenosine A2A receptor gene expression in a model of binge eating in the amygdaloid complex of female rats / Micioni Di Bonaventura, M. V.; Pucci, M.; Giusepponi, M. E.; Romano, A.; Lambertucci, C.; Volpini, R.; Micioni Di Bonaventura, E.; Gaetani, S.; Maccarrone, M.; D'Addario, C.; Cifani, C.. - In: JOURNAL OF PSYCHOPHARMACOLOGY. - ISSN 0269-8811. - 33:12(2019), pp. 1550-1561. [10.1177/0269881119845798]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1402421
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