Increased sensitivity to the hyperphagic effect of Nociceptin/Orphanin FQ after caloric restriction in female rats

Nociceptin/orphanin FQ (N/OFQ) is a functional antagonist of corticotrophin releasing factor (CRF), the main mediator of the stress response, at doses lower than those hyperphagic. Stress represents a key determinant of binge eating (BE) for highly palatable food (HPF). In relation to the anti-stress properties of N/OFQ, the present study evaluated its effect on BE evoked in female rats by three 8-day cycles of food restriction/re-feeding followed by acute stress on day 25. Four groups were used: rats normally fed and not stressed, rats normally fed but stressed, rats exposed to cycles of restriction/re-feeding but not stressed, rats exposed to cycles of restriction/re-feeding and then stressed. Only restricted and stressed rats exhibited BE on HPF. Intracerebroventricular (ICV) injections of N/OFQ, 0.125-0.25 nmol/rat, slightly attenuated and 0.5 nmol/rat significantly reduced it, while no reduction was observed at 1 nmol/rat. In the second experiment, N/OFQ 1 nmol/rat significantly increased HPF intake in rats exposed to food restrictions, but did not modify it in non restricted rats. Also Neuropeptide Y (ICV) at doses inactive in non restricted rats, elicited hyperphagia in restricted rats. In situ hybridization experiments showed that food restrictions increased NOP receptor mRNA in the ventromedial hypothalamus and modified ppN/OFQ mRNA in the bed nucleus of the stria terminalis and ventral tegmental area. These findings demonstrate that low doses of N/OFQ reduce BE, while higher dose (1 nmol/rat) does not reduce BE, apparently because it increases HPF owing to upregulation of the N/OFQ system in response to food restriction.