A NEW GRELIN RECEPTOR ANTAGONIST AGRELAX REDUCES EMOTIONAL OVEREATING CAUSED BY STIMULATION OF THE LATERAL HYPOTHALAMUS REWARD ZONE IN WELL-FED RATS

Abstract

Relevance. Ghrelin receptor antagonists hold promise for the treatment of eating disorders. The reward zone of the lateral hypothalamus has been proposed as a target mediating the effects of the ghrelin system in emotional overeating. The aim was to study the effects of a new ghrelin receptor antagonist agrelax on emotional overeating induced by stimulation of the reward zone of the lateral hypothalamus in well-fed rats. Materials and methods. Male Wistar rats were trained self-stimulation in a Skinner box. After training, a feeder was placed in the Skinner box and a food conditioned reflex was developed in rats for 5 days. Next, we studied the reaction of food self-deprivation, i.e. behavior under conditions of choice of self-stimulation or food intake. Results. The reaction of food self-deprivation, when the animals did not approach the feeder, was observed at a value more than 10% of threshold current. Self-stimulation of the lateral hypothalamus with threshold current caused numerous approaches to the feeder and food intake. Sulpiride, a dopamine D2/D3 antagonist (5 and 20 mg/kg ip), administered to well-fed rats, reduced both feeding behavior and intensity of self-stimulation in the food self-deprivation test at thresholds current. The ghrelin receptor antagonists [D-LYS3]-GHRP-6 and the novel antagonist agrelax (1 g/l, 20 l intranasally) also reduced both feeding behavior and intensity of self-stimulation under these conditions. Conclusion. Ghrelin and dopamine receptors are involved in emotional overeating. A novel ghrelin receptor antagonist agrelax reduces emotional overeating induced by activation of the lateral hypothalamic reward system. Because emotional overeating is strongly associated with clinical eating disorders such as bulimia and binge eating disorder, the use of ghrelin antagonists to treat and prevent this problem is promising.