Reduction of compulsive overeating in rats caused by maternal deprivation in early ontogenesis with the use of a new ghrelin receptor antagonist agrelax
Andrey А. Lebedev , Sarng S. Pyurveev , Natalia D. Nadbitova , Aleksey V. Lizunov , Eugenii R. Bychkov , Valeriya V. Lukashova , Natalia R. Evdokimova , Maria A. Netesa , Viktor A. Lebedev , Petr D. Shabanov
Reviews on Clinical Pharmacology and Drug Therapy ›› 2023, Vol. 21 ›› Issue (3) : 255 -262.
Reduction of compulsive overeating in rats caused by maternal deprivation in early ontogenesis with the use of a new ghrelin receptor antagonist agrelax
BACKGROUND: Factors that may trigger episodes of binge eating include mental and physical stress, dietary restrictions of high-calorie foods. In a rodent model it has been shown that intermittent consumption of high-calorie foods causes binge eating regardless of body weight gain.
AIM: To investigate the effect of a novel ghrelin receptor antagonist Agrelax on binge eating in in adult rats after maternal deprivation in early ontogeny.
MATERIALS AND METHODS: Animals were weaned for 180 min from day 2 to day 12 after birth; males 90–100 days of age were used in the experiments. In the development of binge eating, animals received a high-carbohydrate diet (Nutella paste — based chocolate mixture) for 1 h every day or every third day for 1.5 months. Fifteen minutes before feeding, the chocolate paste was placed within 5 cm of reach with visual contact. Agrelax, a novel ghrelin receptor antagonist, was administered intranasally 1µg/1µl, 20µl for 7 days.
RESULTS: Maternal deprivation induced bindge eating of high-calorie foods in adult rats. When chocolate was given 3 times a week, its consumption increased (p < 0.001) in the maternal deprivation group relative to the control group. After a course of administration of agrelax, chocolate consumption did not differ significantly from that in the control group. The daily consumption of standard food did not differ relative to the control group both before and after the course of agrelax administration. When chocolate was given daily, the maternal deprivation rats did not develop food addiction. At the same time agrelax did not induce a change in chocolate consumption relative to the control group.
CONCLUSIONS: The findings suggest new ways to synthesize pharmacological agents of peptide nature based on ghrelin and its antagonists for correction of food addiction caused by psychogenic stresses in ontogenesis.
bindge eating / maternal deprivation / agrelax / ghrelin
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