Coadministration antagonist dopamine receptor D4 with agonist CB2 receptor decreases binge-like intake of palatable food in mice

Luis Miguel Rodríguez-Serrano ^* Ana Paola López-Castillo María Cristina Cabrera-Mejía Ana Sofía Cedillo-Figueroa Nyahn Zepeda-Ortigosa Carolina Carregha-Lozano María Elena Chávez-Hernández ^*

• Facultad de Psicología, Anahuac University of North Mexico, Huixquilucan de Degollado, México, Mexico

Introduction: Food intake is regulated by two systems: homeostatic and hedonic. A disbalance between both induces overconsumption such as binge eating disorder (BED) and a dysregulation in the dopamine reward system. The cannabinoid type 2 receptor (CB2R) has been identified in dopamine neurons which may play important roles in motivated behaviors such as food intake. Nevertheless, the interaction of the dopamine D4 (DRD4) receptor with CB2R in binge-like intake has not yet been identified. Therefore, the present study aims to evaluate the intraperitoneal administration of DRD4 antagonist (L-745870), as well as the coadministration of DRD4 antagonist with CB2R agonist (HU308) or antagonist (AM630), on binge-like intake of PF in male adult mice. Methods: We used thirty-four C57BL6/J male adult mice; all animals were housed individually and had ad libitum access to a standard diet (SD) and water. To evaluate binge-like intake, the animals had 1h access to palatable food (PF) for twelve baseline binge eating test (BET) sessions. Mice were then randomly assigned to the following treatment groups: 1) vehicle; 2) L-745870; 3) L-745870-HU308, 4) L-745870+AM630 to evaluate the effect for three additionally BET sessions. Results: Our results show that DRD4 antagonist reduced binge-like intake of PF, and that a coadministration of CB2R agonist induced a more pronounced reduction of binge-like intake. Conclusion: These results suggest an interaction between the dopaminergic and endocannabinoid systems in the modulation of binge-like intake of PF in adult mice, where CB2R activation participates modulating reward pathways and reducing binge-like behavior Abbreviations