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
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 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.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"28 1","pages":"0"},"PeriodicalIF":0.0000,"publicationDate":"2023-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Reviews on Clinical Pharmacology and Drug Therapy","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.17816/rcf562841","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
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Abstract

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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使用一种新的生长素受体拮抗剂agrelax,减少个体发育早期母性剥夺引起的大鼠强迫性暴饮暴食
背景:可能引发暴饮暴食发作的因素包括精神和身体压力,高热量食物的饮食限制。在一个啮齿类动物模型中,已经证明间歇性地摄入高热量食物会导致暴饮暴食,而不管体重是否增加。目的:探讨新型胃饥饿素受体拮抗剂Agrelax对母性剥夺后成年大鼠暴饮暴食的影响。材料与方法:动物出生后第2天至第12天断奶180 min;试验选用90 ~ 100日龄雄性。在暴饮暴食的发展过程中,动物每天或每三天接受1小时的高碳水化合物饮食(以Nutella酱为基础的巧克力混合物),持续1.5个月。喂食前15分钟,将巧克力糊放置在视觉可触及的5厘米范围内。Agrelax是一种新型胃饥饿素受体拮抗剂,经鼻给予1g/ 11,201,连续7天。 结果:母性剥夺诱导成年大鼠对高热量食物的束缚进食。当每周给3次巧克力时,与对照组相比,母亲剥夺组的巧克力摄入量增加了(p < 0.001)。在服用一段时间的放松剂后,巧克力的摄入量与对照组没有显著差异。在给药前后,标准食品的日食用量与对照组相比无显著差异。当每天给予巧克力时,母性剥夺大鼠没有产生食物成瘾。与此同时,相对于对照组,agrelax并没有引起巧克力摄入量的变化。结论:本研究结果提示以胃饥饿素及其拮抗剂为基础合成肽类药物,以纠正个体发育过程中心因性应激引起的食物成瘾。
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