Nociceptin receptor antagonist SB 612111 decreases high fat diet binge eating

Abstract

Binge eating is a dysregulated form of feeding behavior that occurs in multiple eating disorders including binge-eating disorder, the most common eating disorder. Feeding is a complex behavioral program supported through the function of multiple brain regions and influenced by a diverse array of receptor signaling pathways. Previous studies have shown the overexpression of the opioid neuropeptide nociceptin (orphanin FQ, N/OFQ) can induce hyperphagia, but the role of endogenous nociceptin receptor (NOP) in naturally occurring palatability-induced hyperphagia is unknown. In this study we adapted a simple, replicable form of binge eating of high fat food (HFD). We found that male and female C57BL/6J mice provided with daily one-hour access sessions to HFD eat significantly more during this period than those provided with continuous 24 hour access. This form of feeding is rapid and entrained. Chronic intermittent HFD binge eating produced hyperactivity and increased light zone exploration in the open field and light-dark assays respectively. Treatment with the potent and selective NOP antagonist SB 612111 resulted in a significant dose-dependent reduction in binge intake in both male and female mice, and, unlike treatment with the serotonin selective reuptake inhibitor fluoxetine, produced no change in total 24-hour food intake. SB 612111 treatment also significantly decreased non-binge-like acute HFD consumption in male mice. These data are consistent with the hypothesis that high fat binge eating is modulated by NOP signaling and that the NOP system may represent a promising novel receptor to explore for the treatment of binge eating.

Sex Differences in Demand for Highly Palatable Foods: Role of the Orexin System

“…In clinical studies, females report a higher preference for high-fat, high-sugar foods and carbohydrates ( Asarian and Geary, 2013 ) as well as enhanced neuronal responses to palatable foods in key brain reward regions ( Cordeira et al, 2010 ; Legget et al, 2018 ). These findings are generally recapitulated in animal studies; female rats consume more palatable food and escalate their intake of palatable food at a faster rate compared with males ( Babbs et al, 2011 ; Carlin et al, 2016 ; Hardaway et al, 2016 ). Thus, rodents offer a valuable model system to interrogate the biological factors that underpin sex differences in eating behavior.…”

Adaptive Changes in the Central Control of Energy Homeostasis Occur in Response to Variations in Energy Status

“…Providing further support for the intrinsic contribution of endogenous N/OFQ/NOP signaling in the pathogenesis of obesity and eating disorders, systemic administration of LY2940094 reduced intake of HFD in diet-induced obese rats and mice, and also improved metabolic parameters by reducing the respiratory quotient in mice with access to HFD in their metabolic feeding chamber [ 195 ]. In relation to N/OFQ and binge-feeding, systemic treatment with the selective NOP antagonist SB 612111 produced a dose-dependent decrease in intermittent HFD binge eating, but not a change in the total 24-h food intake of mice who were either on an intermittent-HFD or continuous-HFD feeding regimen [ 196 ].…”

The Melanocortin System behind the Dysfunctional Eating Behaviors

“…[ 12 , 53 , 54 , 55 ]). In addition, another functional interaction of the melanocortin system in the ARC nucleus is with the orexigenic neuropeptide Nociceptin/Orphanin FQ [ 56 , 57 ], which exerts an inhibitory influence on α-MSH cells [ 58 ], and is strictly involved in stress mechanisms [ 59 , 60 ] and binge eating behavior [ 56 , 61 , 62 , 63 , 64 ].…”