Effects of the new ghrelin receptor antagonist agrelax on compulsive overeating induced by acute and chronic stress in rats

Abstract

BACKGROUND: Intense and prolonged stress can be detrimental to both psychological and physical health. Stress often leads to the development or worsening of compulsive overeating. Compulsive overeating is characterized by recurrent episodes of consuming large amounts of food, accompanied by a sense of loss of control. AIM: To study the effects of the ghrelin receptor antagonist Agrelax on compulsive overeating induced by acute and chronic stress in rats. MATERIALS AND METHODS: The study involved 150 male and 15 female Wistar rats. To simulate compulsive overeating, the animals received a high-calorie mixture based on chocolate paste three times a week, while maintaining free access to standard food and water. Compulsive behavior was assessed using the marble burying test. Different groups of animals were exposed to various stressors, including maternal deprivation, limb electrical stimulation, partial sensory and complete social isolation, and acute vital stress. Agrelax, a ghrelin receptor antagonist, was administered intranasally at a dose of 1 μg/μL, 10 μL in each nostril, for 7 days. RESULTS: Compulsive behavior was evaluated using the marble burying test. The experimental group on a high-calorie diet buried significantly more marbles than the control group (p 0.01). After a 7-day course of Agrelax, the number of buried marbles significantly decreased, reaching the control group values (p 0.05). A model of compulsive overeating in rats was successfully developed by providing high-calorie food three times a week. After a 7-day course of Agrelax, the consumption of high-calorie food significantly decreased (p 0.05). Limb electrical stimulation significantly increased the consumption of high-calorie food (p 0.05). After a 7-day course of Agrelax, the consumption of high-calorie food significantly decreased (p 0.01). Maternal deprivation stress significantly increased the consumption of high-calorie food (p 0.001). After a 7-day course of Agrelax, the consumption of high-calorie food decreased, reaching the control group values. In animals raised under partial sensory and complete social isolation, Agrelax did not significantly reduce the consumption of high-calorie food. In animals subjected to acute vital stress, Agrelax did not reduce the consumption of high-calorie food. CONCLUSIONS: The data obtained suggest new ways for synthesizing peptide pharmacological agents based on ghrelin and its antagonists to treat eating disorders.