Laboratory of Addictive Disorders, Departments of Pharmacology and Psychiatry, Boston University School of Medicine, Boston, MA, USA.
Neuropsychopharmacology. 2013 Nov;38(12):2456-66. doi: 10.1038/npp.2013.147. Epub 2013 Jun 10.
Highly palatable foods and dieting are major contributing factors for the development of compulsive eating in obesity and eating disorders. We previously demonstrated that intermittent access to palatable food results in corticotropin-releasing factor-1 (CRF1) receptor antagonist-reversible behaviors, which include excessive palatable food intake, hypophagia of regular chow, and anxiety-like behavior. However, the brain areas mediating these effects are still unknown. Male Wistar rats were either fed chow continuously for 7 days/week (Chow/Chow group), or fed chow intermittently 5 days/week, followed by a sucrose, palatable diet 2 days/week (Chow/Palatable group). Following chronic diet alternation, the effects of microinfusing the CRF1 receptor antagonist R121919 (0, 0.5, 1.5 μg/side) in the central nucleus of the amygdala (CeA), the basolateral nucleus of the amygdala (BlA), or the bed nucleus of the stria terminalis (BNST) were evaluated on excessive intake of the palatable diet, chow hypophagia, and anxiety-like behavior. Furthermore, CRF immunostaining was evaluated in the brain of diet cycled rats. Intra-CeA R121919 blocked both excessive palatable food intake and anxiety-like behavior in Chow/Palatable rats, without affecting chow hypophagia. Conversely, intra-BlA R121919 reduced the chow hypophagia in Chow/Palatable rats, without affecting excessive palatable food intake or anxiety-like behavior. Intra-BNST treatment had no effect. The treatments did not modify the behavior of Chow/Chow rats. Immunohistochemistry revealed an increased number of CRF-positive cells in CeA--but not in BlA or BNST--of Chow/Palatable rats, during both withdrawal and renewed access to the palatable diet, compared with controls. These results provide functional evidence that the CRF-CRF1 receptor system in CeA and BlA has a differential role in mediating maladaptive behaviors resulting from palatable diet cycling.
高可口性食物和节食是肥胖和饮食失调中强迫性进食发展的主要促成因素。我们之前的研究表明,间歇性获得可口食物会导致促肾上腺皮质释放因子-1 (CRF1) 受体拮抗剂逆转行为,包括过度摄入可口食物、常规食物摄入量减少和焦虑样行为。然而,介导这些效应的大脑区域仍不清楚。雄性 Wistar 大鼠要么连续 7 天/周喂食标准食物(Chow/Chow 组),要么连续 5 天/周喂食标准食物,然后 2 天/周喂食蔗糖可口食物(Chow/Palatable 组)。在慢性饮食交替后,评估了在中央杏仁核(CeA)、杏仁基底外侧核(BlA)或终纹床核(BNST)中微注射 CRF1 受体拮抗剂 R121919(0、0.5、1.5μg/侧)对摄入过多可口食物、食物摄入量减少和焦虑样行为的影响。此外,还评估了饮食循环大鼠大脑中的 CRF 免疫染色。CeA 内 R121919 阻断了 Chow/Palatable 大鼠过度摄入可口食物和焦虑样行为,而不影响食物摄入量减少。相反,BlA 内 R121919 减少了 Chow/Palatable 大鼠的食物摄入量减少,而不影响过度摄入可口食物或焦虑样行为。BNST 治疗没有效果。这些治疗方法没有改变 Chow/Chow 大鼠的行为。免疫组织化学显示,与对照组相比,Chow/Palatable 大鼠在退出和重新获得可口食物时,CeA 中的 CRF 阳性细胞数量增加,而 BlA 或 BNST 中的 CRF 阳性细胞数量没有增加。这些结果提供了功能证据,表明 CeA 和 BlA 中的 CRF-CRF1 受体系统在介导可口食物循环引起的适应不良行为方面具有不同的作用。