利用一种新的 OX1 受体拮抗剂纠正大鼠在幼年期被剥夺母性后的强迫性暴食症

Andrey А. Lebedev, S. S. Pyurveev
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摘要

背景。强迫性暴饮暴食(神经性贪食症、暴饮暴食症)是进食障碍的基础,在《国际疾病分类》(ICD-11)和《美国疾病分类与诊断》(DSM-5)中被列为非化学性成瘾的一种表现形式。它是一种冲动性和强迫性行为障碍。肥胖症和进食障碍的特点是强迫性进食,类似于药物使用障碍的强迫性吸毒。研究目的研究 OX1 受体拮抗剂 anthorex 对母体剥夺模型中动物强迫性暴食的影响。材料和方法。性成熟雄性大鼠出生后第 2 至 12 天与母亲分离 3 小时,每隔 3 天喂食高碳水化合物食物 1 小时,持续 45 天。在这种情况下,在喂食前 15 分钟将高热量食物放置在可触及的 5 厘米范围内,并进行视觉接触。奥利欣受体拮抗剂Anthorex以1微克/1微升、20微升的剂量经鼻给药7天。结果间歇性食用高热量食物会导致大鼠强迫性暴食。与对照组相比(P 0.001),在我们的模型中,性成熟动物在早期发育过程中经历了母体剥夺后,强迫性暴食高碳水化合物食物的迹象增加。与此同时,标准压块饲料的消耗量没有变化。与对照组相比,在断奶后间歇性食用高热量食物的条件下,鼻内给药 OX1 受体拮抗剂 anthorex 可减少大鼠强迫性暴食的表现(P 0.05)。在服用奥曲肽拮抗剂前后,标准食物的摄入量与对照组相比没有差异。结论这项研究提出了研究和合成基于奥曲肽及其拮抗剂的多肽药物的新方法,以纠正儿童期慢性应激引起的强迫性暴食。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Correction of compulsive overeating in rats after maternal deprivation in early age using a new antagonist of OX1 receptors
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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