A new ghrelin receptor antagonist agrelax participates in the control of emotional-explorative behavior and anxiety in rats

Lebedev, A. A.; Lukashkova, Valeriya V.; Pshenichnaya, Anna G.; Bychkov, Eugenii R.; Lebedev, Viktor A.; Rusanovsky, V. V.; Shabanov, Petr D.

doi:10.17816/phbn321624

Psychopharmacology & biological narcology

2023

DOI: 10.17816/phbn321624

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A new ghrelin receptor antagonist agrelax participates in the control of emotional-explorative behavior and anxiety in rats

A. A. Lebedev

Valeriya V. Lukashkova

Anna G. Pshenichnaya

et al.

Abstract: BACKGROUND: Currently, no study has investigated on the role of ghrelin in the reinforcing system and emotional behavior. Previously, we examined the properties of GHSR1A antagonist [D-Lys3]-GHRP-6 to reduce negative emotional states caused by stress. AIM: To study the involvement of a new peptide antagonist of the GHSR1A receptor agrelax in the control of emotionalexploratory behavior and anxiety in rats. MATERIALS AND METHODS: Experiments were performed on 42 male Wistar rats. The behavior of rat… Show more

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Cited by 5 publications

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Correction of compulsive overeating in rats after maternal deprivation in early age using a new antagonist of OX1 receptors

Lebedev,

Pyurveev,

Nadbitova

et al. 2024

Psychopharmacology & biological narcology

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Background. Compulsive overeating (bulimia nervosa, binge eating disorder) is the basis of eating disorders and is included in ICD-11 and DSM-5 as a manifestation of a non-chemical form of addiction. It is a behavioral disorder of impulsivity and compulsivity. Obesity and eating disorders are characterized by compulsive food consumption, similar to the compulsive drug use of substance use disorders. Aim. Study of the effect of the OX1 receptor antagonist anthorex on compulsive overeating in animals in a model of maternal deprivation. Materials and methods. Sexually mature male rats, which were separated from their mother for 3 hours after birth from days 2 to 12, were fed a high-carbohydrate diet every third day for 1 hour for 45 days. In this case, high-calorie food was placed within 5 cm of reach with visual contact 15 minutes before feeding. Orexin receptor antagonist Anthorex was administered intranasally for 7 days at a dose of 1 µg/1 µl, 20 µl. 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 OX1 receptor antagonist anthorex reduced the manifestations of compulsive overeating in rats after weaning under conditions of intermittent consumption of high-calorie food compared to the control group (p 0.05). Consumption of standard food did not differ relative to the control group, both before and after the course of administration of the orexin antagonist. Conclusion. The work suggest new ways of studying and synthesizing peptide drugs based on orexin and its antagonists for the correction of compulsive overeating caused by chronic stress in ontogenesis.

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Correction of compulsive overeating in rats after maternal deprivation in early age using a new antagonist of OX1 receptors

Lebedev,

Pyurveev,

Nadbitova

et al. 2024

Psychopharmacology & biological narcology

View full text Add to dashboard Cite

show abstract

Reduction of compulsive overeating in rats caused by maternal deprivation in early ontogenesis with the use of a new ghrelin receptor antagonist agrelax

Lebedev,

Pyurveev,

Nadbitova

et al. 2023

Rev Clin Pharm Drug Ther

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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 90100 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 1g/1l, 20l 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.

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A new ghrelin receptor antagonist, agrelax, reduces emotional overeating caused by the stimulation of the lateral hypothalamus reward zone in well-fed rats

Lebedev,

Bychkov,

Lukashkova

et al. 2024

Rev Clin Pharm Drug Ther

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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.

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A new ghrelin receptor antagonist agrelax participates in the control of emotional-explorative behavior and anxiety in rats

Cited by 5 publications

References 24 publications

Correction of compulsive overeating in rats after maternal deprivation in early age using a new antagonist of OX1 receptors

Correction of compulsive overeating in rats after maternal deprivation in early age using a new antagonist of OX1 receptors

Reduction of compulsive overeating in rats caused by maternal deprivation in early ontogenesis with the use of a new ghrelin receptor antagonist agrelax

A new ghrelin receptor antagonist, agrelax, reduces emotional overeating caused by the stimulation of the lateral hypothalamus reward zone in well-fed rats

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