Antorex, a new antagonist of orexin receptors, reduces binge eating in rats caused by weaning from mother in early ontogenesis

Abstract

Background. Obesity and eating disorders are characterized by compulsive food consumption, similar to compulsive drug use in substance use disorders. It is believed that overeating in order to relieve a negative emotional state is caused by two processes: a decrease in sensitivity to reward and the emergence of negative affect. Aim. To study the effect of a new OХ1 receptor antagonist «Antorex» on compulsive overeating in animals that experienced maternal deprivation at an early age. Materials and methods. Mature male rats, who were weaned from their mother for 3 hours after birth from day 2 to 12, received a high-carbohydrate diet for 45 days every third day for 1 hour. At the same time, high-calorie food was placed within 5 cm of visual contact 15 minutes before feeding. Antorex, an orexin receptor antagonist, was administered intranasally for 7 days at a dose of 1 mcg/mcl, 20 ?l. Results. Intermittent consumption of high-calorie foods caused compulsive overeating in rats. Sexually mature animals that experienced deprivation from their mother in early ontogenesis showed increased signs of compulsive overeating of high-carbohydrate foods in our model relative to the control (p <0.001). At the same time, the consumption of standard briquetted feed did not change. Intranasal administration of the OХ1 receptor antagonist «Antorex» reduced the manifestations of compulsive overeating in rats after weaning in conditions of intermittent consumption of high-calorie food compared with the control group (p <0.05). The consumption of standard feed did not differ relative to the control group both before and after the course of antorex administration. Conclusion. Thus, the data obtained in the course of the work suggest new ways to study and synthesize peptide-based drugs based on orexin and its antagonists for the correction of compulsive overeating caused by chronic stress in ontogenesis.