CRF–CRF1 Receptor System in the Central and Basolateral Nuclei of the Amygdala Differentially Mediates Excessive Eating of Palatable Food

Abstract

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 (CRF 1 ) 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 CRF 1 receptor antagonist R121919 (0, 0.5, 1.5 mg/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-CRF 1 receptor system in CeA and BlA has a differential role in mediating maladaptive behaviors resulting from palatable diet cycling.

Role of Bed Nucleus of the Stria Terminalis Corticotrophin-Releasing Factor Receptors in Frustration Stress-Induced Binge-Like Palatable Food Consumption in Female Rats with a History of Food Restriction

“…However, in contrast to our findings that implicate BNST CRF receptors in stress-induced binge eating, Iemolo et al (2013) reported, using their binge-eating model, that the critical site for CRF modulation of binge eating is central amygdala, not BNST. A question for future research is whether Figure 2.…”

“…Evidence for the efficacy of CRF1 receptor antagonists in psychiatric disorders has not yet been documented, and several clinical trials for depression and anxiety reported negative results (Zorrilla and Koob, 2010;Zorrilla et al, 2013b). Against this background, our data and those of Cottone, Sabino, and colleagues (Cottone et al, 2009;Iemolo et al, 2013) suggest a potential novel use of CRF1 receptor antagonists in the treatment of stress-related bingeeating disorders.…”

Rimonabant Precipitates Anxiety in Rats Withdrawn from Palatable Food: Role of the Central Amygdala

“…The reduced effectiveness of CB 1 receptor blockade on excessive palatable food intake is consistent with what we previously published (Parylak et al, 2012). Compulsive eating observed here is analogous to the behavior observed in other animal models of drug dependence, which is characterized by the relief of anxiety by performing the compulsive behavior (Cottone et al, 2009b;Iemolo et al, 2013;Koob, 2009;Koob and Volkow, 2010). However, it is important to mention that in preclinical research compulsive behavior is also defined as a behavior, which occurs in spite of negative consequences (Belin et al, 2008;Davis et al, 2010;Dore et al, 2013b;Johnson and Kenny, 2010).…”

Pituitary Adenylate Cyclase-Activating Peptide in the Central Amygdala Causes Anorexia and Body Weight Loss via the Melanocortin and the TrkB Systems

“…Microinfusion procedure. Drugs were microinfused as previously described (Blasio et al, 2014;Dore et al, 2013;Iemolo et al, 2013). The injector projected 2 mm beyond the tip of the guide cannula.…”