Hypothalamic CRF1 receptor mechanisms are not sufficient to account for binge‐like palatable food consumption in female rats

Abstract

Rationale The interaction between dieting and stress is a key factor for triggering binge episodes on palatable food in human binge eaters. Corticotropin releasing factor (CRF) mechanisms are known to play a pivotal role in the regulation of this maladaptive behavior. 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/refeeding 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.

Oleoylethanolamide decreases frustration stress-induced binge-like eating in female rats: a novel potential treatment for binge eating disorder

“…In agreement with this notion, and overlapping with the trend of c-Fos induction in the AMY, we found that OEA decreased CRF mRNA level in the CeA of R + S rats, without producing any effect on the PVN, and without affecting the same parameters in NR + S rats. The results confirm previous findings demonstrating that hypothalamic CRF system is not sufficient to account for binge-like HPF consumption in our BED model [ 47 , 48 ], and that CRF in the CeA plays a key role in other models of excessive palatable food consumption [ 67 – 69 ]. These latter observations were further supported by the findings that treatments with CRF antagonists can prevent binge eating by interacting with CRF receptors in bed nucleus of the stria terminalis [ 47 , 48 , 70 ] and CeA [ 67 – 69 ], rather than at hypothalamic levels.…”

“…We previously demonstrated a crucial role of oxytocinergic neurotransmission in mediating the hypophagic effect of OEA [ 29 ], as well as the pivotal role played by CRF system in sustaining binge eating behavior in the experimental model used in the present study [ 47 ]. Since both oxytocin and CRF can be affected by stress and food intake, we assessed the “pure” effects of OEA on stress response without the potential impact of caloric consumption, to evaluate whether the anti-bingeing effects of OEA might be attributed to a reduced effect of stress exposure.…”

“…The procedure for binge eating induction was performed according to our previous studies [ 37 , 47 , 48 ]. Briefly, two groups of female rats were housed individually in metal cages (30 × 30 × 30 cm) and exposed (or not exposed) for 24 days to three 8-day cycles of intermittent food restriction (66% of chow intake on days 1–4 and free feeding on days 5–8 of each cycle), during which they were given access to HPF for 2 h during the light cycle between 10:00 a.m. and 12:00 a.m. (2 h after the onset of the light cycle) on days 5–6 and 13–14 of the first two cycles (total of four exposures).…”

RLN3/RXFP3 Signaling in the PVN Inhibits Magnocellular Neurons via M-like Current Activation and Contributes to Binge Eating Behavior

“…RXFP3 activation in the PVN is necessary for the occurrence of BE behavior RLN3/RXFP3 signaling has been linked to binge-like eating (Lenglos et al, 2013;Calvez et al, 2016b); so to further assess the involvement of PVN RXFP3 in this phenomenon, we used an established rat model of BE (Cifani et al, 2009;Piccoli et al, 2012;Micioni Di Bonaventura et al, 2017) combined with intra- Figure 4. NI RLN3 neurons innervate the PVN and its adjacent areas, with a higher fiber density in female than in male rats.…”

Food Addiction and Binge Eating: Lessons Learned from Animal Models

“…Indeed, frustration stress manipulation increased BNST neuronal activity and CRF receptors of BNST seem to have a critical role in stress-induced binge eating disorder [ 201 ]. The role of other extra-hypothalamic CRF1 receptors, as those in central amygdala, has been also implicated in development of binge eating [ 202 ]. The early emotional environment also impacts on eating behaviour.…”