一种新型 grelin 受体拮抗剂 Agrelax 可减少刺激下丘脑外侧奖赏区对饱食大鼠造成的情绪性暴饮暴食

Andrey А. Lebedev, Evgenii Bychkov, Viktoria Lukaskova, Viktor Lebedev, N. Efimov, Petr Shabanov
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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. 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引用次数: 0

摘要

相关性。胃泌素受体拮抗剂有望治疗饮食失调症。外侧下丘脑的奖赏区被认为是调节胃泌素系统对情绪性暴食影响的靶点。 本研究的目的是研究一种新型胃泌素受体拮抗剂 agrelax 对刺激下丘脑外侧奖赏区诱发饱食大鼠情绪性暴食的影响。 材料和方法雄性 Wistar 大鼠在斯金纳箱中接受自我刺激训练。训练结束后,在斯金纳箱中放置喂食器,并在 5 天内培养大鼠的食物条件反射。接下来,我们研究了食物自我剥夺的反应,即在选择自我刺激或食物摄入条件下的行为。 研究结果当动物不接近喂食器时,食物自我剥夺的反应在阈值电流的10%以上时出现。用阈值电流自我刺激外侧下丘脑会使动物多次接近喂食器并摄入食物。多巴胺 D2/D3 拮抗剂舒必利(5 毫克和 20 毫克/千克 ip)给喂养良好的大鼠服用后,可减少阈值电流下食物自我剥夺试验中的摄食行为和自我刺激强度。胃泌素受体拮抗剂[D-LYS3]-GHRP-6和新型拮抗剂agrelax(1克/升,20升鼻内注射)也能在这些条件下减少摄食行为和自我刺激强度。 结论胃泌素和多巴胺受体与情绪性暴食有关。一种新型胃泌素受体拮抗剂agrelax可减少激活下丘脑外侧奖赏系统引起的情绪性暴食。由于情绪性暴食与暴食症和暴饮暴食症等临床饮食失调症密切相关,因此使用胃泌素拮抗剂治疗和预防这一问题很有前景。
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A NEW GRELIN RECEPTOR ANTAGONIST AGRELAX REDUCES EMOTIONAL OVEREATING CAUSED BY STIMULATION OF THE LATERAL HYPOTHALAMUS REWARD ZONE IN WELL-FED RATS
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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