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.
Bibliographical noteFunding Information:
This work was supported by the Department of Veterans Affairs, by National Institute of Drug Abuse Grant DA-03999 and by the National Institutes of Diabetes and Digestive and Kidney Disease Grant DK-42698 and P30 DK-50456.
- Nociceptin/orphanin FQ