Functional interaction between nociceptin/orphanin FQ and alpha-melanocyte-stimulating hormone in the regulation of feeding.
Nociceptin/orphanin FQ (N/OFQ), an endogenous agonist of the opioid N/OFQ (NOP) receptor, increases food intake when administered centrally. As N/OFQ is part of a larger neural network that governs consummatory behavior, presumably its orexigenic properties stem from interplay with other neuropeptidergic components of the feeding-related circuitry. One such peptide may be the ligand of the melanocortin-3 and -4 receptors, alpha-melanocyte-stimulating hormone (alpha-MSH), which is known to inhibit food intake. The aim of the present study was to establish whether there is a functional "interaction" between N/OFQ and alpha-MSH in the regulation of feeding. By using double immunostaining for c-Fos and alpha-MSH, we found that intracerebroventricular (i.c.v.) injection of N/OFQ at a 10nmol dose that moderately prolongs deprivation-induced food intake in rats, decreases activation of alpha-MSH neurons involved in feeding termination. However, i.c.v. injections of alpha-MSH at doses previously established to reduce deprivation-induced feeding, do not decrease hyperphagia generated by N/OFQ in ad libitum-fed animals. Our results suggest that while alpha-MSH does not appear to modify the orexigenic response to N/OFQ in sated rats, the NOP receptor ligand promotes a decrease in activation of neurons synthesizing the anorexigenic peptide, alpha-MSH, at the time of re-feeding. Thus, to some degree, the stimulatory effect of N/OFQ on consumption may arise from this peptide's inhibitory influence on activity of anorexigenic pathways containing alpha-MSH.
Minnesota Obesity Center, VA Medical Center, Minneapolis, MN 55417, USA.
Eric M
EM
Bomberg
Martha K
MK
Grace
Allen S
AS
Levine
Pawel K
PK
Olszewski
D000818:Animals; D002552:Cerebral Ventricles / Q000378:metabolism; D004435:Eating; D005247:Feeding Behavior; D005508:Food Deprivation; D008297:Male; D009474:Neurons / Q000378:metabolism; D018847:Opioid Peptides / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000521:alpha-MSH / Q000502:physiology*; D000097629:Nociceptin
D018847:Opioid Peptides; D016760:Proto-Oncogene Proteins c-fos; D000521:alpha-MSH; D000097629:Nociceptin