The effect of [Phe¹ψ(CH₂-NH)Gly²]-nociceptin(1-13)NH₂ on feeding and c-Fos immunoreactivity in selected brain sites

Nociceptin/orphanin FQ (N/OFQ) is an endogenous ligand of the ORL1 receptor. N/OFQ, when administered centrally, stimulates feeding in a fashion similar to other opioids. Intracerebroventricular administration of N/OFQ induces changes in c-Fos immunoreactivity in several feeding-related brain sites. A synthetic pseudopeptide, [Phe¹ι(CH₂-NH)Gly²]-nociceptin(1-13)- NH₂ (hereafter: [FG]N/OFQ(1-13)NH₂), has been labeled both as an ORL1 agonist and antagonist. The present study was designed to examine the influence of [FG]N/OFQ(1-13)NH₂ on food intake in rats. We also evaluated c- Fos immunoreactivity in those areas of the brain which have been shown to exhibit altered c-Fos expression upon N/OFQ administration. We found that [FG]N/OFQ(1-13)NH₂ increases food consumption in satiated rats. This effect is short-lasting and can be reversed by the opioid antagonist naloxone. Co- administration of [FG]N/OFQ(1-13)NH₂ does not affect orexigenic response to N/OFQ. Intracerebroventricularly-injected [FG]N/OFQ(1-13)NH₂ induces c-Fos expression in the nucleus of the solitary tract, hypothalamic paraventricular and supraoptic nuclei, central nucleus of amygdala, lateral septal and lateral habenular nuclei-brain areas that have been shown to be activated by N/OFQ. These results support the hypothesis that [FG]N/OFQ(1-13)NH₂ acts as an agonist of ORL1 receptor in vivo. (C) 2000 Elsevier Science B.V.