The stress system is well known to play an important role in relapse to drug abuse and is largely controlled by corticotropin releasing hormone receptors (CRHR) and their endogenous ligands. Binge eating behavior resembles some aspects of drug seeking behavior and drug dependence. Stress is well-recognized to be to be a major factor in precipitation of binge eating in individuals with binge eating disorder (BED). We studied the effect of systemic injection of the CRHR1-selective antagonist, R121919, (2,5-dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7-dipropylaminopyrazolo-1,5a-pyrimidine), the corticosterone synthesis inhibitor metyrapone and central amygdala (CeA) injections of the nonselective CRH antagonist D-Phe-CRF(12--41) in rats in which binge eating was evoked by stress and cycles of food restriction. Our results showed that systemic injections of R121919, but not of the metyrapone, blocked binge-like eating behavior. Stress and restriction in rats produced up-regulation of the CRH1 receptor mRNA signal in the bed nucleus of the stria terminalis and CeA. However, this was not observed in the basolateral amygdala (BLA) or in the paraventricular nucleus. Injection of D-Phe-CRF(12--41) in CeA but not in the BLA-blocked binge-like eating behavior. We did not find an effect of metyrapone on binge eating behavior. Our results demonstrate that extra-hypothalamic CRF1 receptors, rather than those involved in endocrine functions, are involved in binge eating and the crucial role of CRH receptors in CeA. CRH 1 receptor antagonism may represent a novel pharmacological treatment for binge-related eating disorders.
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