Caloric restriction increases the sensitivity to the hyperphagic effect of nociceptin/orphanin FQ limiting its ability to reduce binge eating in female rats

Rationale: Nociceptin/Orphanin FQ (N/OFQ) is a functional antagonist of corticotropin releasing factor, the main mediator of the stress response. Stress represents a key determinant of binge eating (BE) for highly palatable food (HPF). Objectives: In relation to the anti-stress properties of N/OFQ, we evaluated its effect on BE. After the observation that episodes of food restriction increase the sensitivity to its hyperphagic effects, the function of NOP receptor and N/OFQ was investigated after cycles of food restrictions. Materials and methods: In BE experiments, four groups were used: rats fed normally and not stressed or stressed, rats exposed to cycles of restriction/re-feeding and then stressed, or not stressed. In the other experiments, two groups were used: rats exposed or not to food restriction. Results: Only restricted and stressed rats exhibited BE for HPF (containing chocolate cream). Intracerebroventricular injections of N/OFQ 0.5 nmol/rat significantly reduced BE. N/OFQ 1 nmol/rat did not reduce BE but significantly increased HPF intake following food restrictions. Cycles of food restriction increased animals’ sensitivity to the hyperphagic effect of N/OFQ for HPF. In situ hybridization studies following food restrictions showed decreased ppN/OFQ mRNA expression in the bed nucleus of the stria terminalis and increased expression of ppN/OFQ and NOP receptor mRNA in the ventral tegmental area and in the ventromedial hypothalamus, respectively. Conclusions: These findings indicate that, N/OFQ slightly reduces BE at low doses, while higher doses increase HPF intake, due to increased sensitivity to its hyperphagic effect following a history of caloric restrictions.