The effect of [Phe(1)psi(CH(2)-NH)Gly(2)]-nociceptin(1-13)NH(2) 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, [Phe(1)iota(CH(2)-NH)Gly(2)]-nociceptin(1-13)-NH(2) (hereafter: [FG]N/OFQ(1-13)NH(2)), 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)NH(2) 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)NH(2) 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)NH(2) does not affect orexigenic response to N/OFQ. Intracerebroventricularly-injected [FG]N/OFQ(1-13)NH(2) 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)NH(2) acts as an agonist of ORL1 receptor in vivo.
Olszewski
P K
PK
Minnesota Obesity Center, Research Service, Veterans Affairs Medical Center (151), Minneapolis, MN 55417, USA.
Grace
M K
MK
Billington
C J
CJ
Levine
A S
AS
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D004435:Eating / Q000187:drug effects*; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D008297:Male; D018847:Opioid Peptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D018847:Opioid Peptides; D010446:Peptide Fragments; D016760:Proto-Oncogene Proteins c-fos; C114149:nociceptin (1-13)-NH2, Phe(1)-psi(CH2-NH)-Gly(2)-