Hypothalamic CRF1 receptor mechanisms are not sufficient to account for binge-like palatable food consumption in female rats
Hypothalamic CRF1 receptor mechanisms are not sufficient to account for binge-like palatable food consumption in female rats
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DOI：
10.1002/eat.22767
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发表时间：
2017-10-01
影响因子：
5.5
通讯作者：
Cifani, Carlo
中科院分区：
文献类型：
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作者：
Di Bonaventura, Maria Vittoria Micioni;Ubaldi, Massimo;Cifani, Carlo
目的：观察全身注射CRF1受体拮抗剂R121919、皮质酮合成抑制剂甲孕酮和非选择性CRF拮抗剂D-Phe-CRF(12-41)对暴食大鼠的影响。方法：雌性大鼠接受或不接受常规食物限制/自由喂养的重复循环，在此期间，它们也被给予有限的可口食物(2 H)。在测试当天，老鼠在不允许进入的情况下接触或不接触美味食物15分钟，然后评估食物摄入量。结果：全身注射R121919阻止了暴饮式进食行为，但不能阻止美替拉酮。限制应激大鼠终纹床核和CEA中CRH1受体mRNA信号上调，而杏仁基底外侧核(BLA)和室旁核中CRH1受体mRNA信号不上调。在CEA中注射D-Phe-CRF(12-41)，但不在BLA阻断的暴饮式进食行为中。讨论：这些发现表明，参与暴饮暴食的是下丘脑外CRF1受体，而不是参与内分泌功能的受体，以及CRF受体在CEA中的关键作用。CRF1受体拮抗剂可能是治疗暴饮暴食相关饮食障碍的一种新的药物治疗方法。
Objective: The present study evaluated the effect of systemic injection of the CRF1 receptor antagonist R121919, the corticosterone synthesis inhibitor metyrapone and central amygdala (CeA) injections of the nonselective CRF antagonist D-Phe-CRF(12-41) in rats in which binge eating was evoked by stress and cycles of food restriction. Method: Female rats were subjected or not to repeated cycles of regular chow food restriction/ad libitum feeding during which they were also given limited access (2 h) to palatable food. On the test day, rats were either exposed or not to the sight of the palatable food for 15 min without allowing access, before assessing food consumption. Results: Systemic injections of R121919, but not of the metyrapone, blocked binge-like eating behavior. Restricted and stressed rats showed up-regulation of crh1 receptor mRNA signal in the bed nucleus of the stria terminalis and CeA but not in basolateral amygdala (BLA) or in the paraventricular nucleus. Injection D-Phe-CRF(12-41) in CeA but not in the BLA-blocked binge-like eating behavior. Discussion: These findings demonstrate that extra-hypothalamic CRF1 receptors, rather than those involved in endocrine functions, are involved in binge eating and the crucial role of CRF receptors in CeA. CRF1 receptor antagonism may represent a novel pharmacological treatment for binge-related eating disorders.