NPY-induced feeding: pharmacological characterization using selective opioid antagonists and antisense probes in rats

• Published in: Peptides (New York, N.Y. : 1980) Vol. 26; no. 7; pp. 1167 - 1175
• Main Authors: Israel, Y., Kandov, Y., Khaimova, E., Kest, A., Lewis, S.R., Pasternak, G.W., Pan, Y.X., Rossi, G.C., Bodnar, R.J.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.07.2005; Elsevier Science
• Subjects: Animals; Appetite Regulation - physiology; Behavior, Animal - drug effects; Biological and medical sciences; Feeding Behavior - drug effects; Fundamental and applied biological sciences. Psychology; Male; Naltrexone; Naltrindole; Narcotic Antagonists - administration & dosage; Narcotic Antagonists - pharmacology; Neuropeptide Y - antagonists & inhibitors; Neuropeptide Y - pharmacology; Nor-binaltorphamine; Oligodeoxyribonucleotides, Antisense - genetics; Oligodeoxyribonucleotides, Antisense - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Opioid - genetics; Vertebrates: endocrinology; β-Funaltrexamine; δ opioid receptor; κ opioid receptor; μ opioid receptor; β-Funaltrexamine; δ opioid receptor; μ opioid receptor; Naltrindole; Naltrexone; Nor-binaltorphamine; κ opioid receptor; Neuropeptide Y; Drug addiction; Feeding behavior; Rat; Opioid receptor; Rodentia; μ Opioid receptor; K opioid receptor; Feeding; Characterization; Vertebrata; Mammalia; Animal; Antagonist; 8 opioid receptor
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2005.01.017

The ability of neuropeptide Y to potently stimulate food intake is dependent in part upon the functioning of μ and κ opioid receptors. The combined use of selective opioid antagonists directed against μ, δ or κ receptors and antisense probes directed against specific exons of the MOR-1, DOR-1, KOR-1 and KOR-3/ORL-1 opioid receptor genes has been successful in characterizing the precise receptor subpopulations mediating feeding elicited by opioid peptides and agonists as well as homeostatic challenges. The present study examined the dose-dependent (5–80 nmol) cerebroventricular actions of general and selective μ, δ, and κ 1 opioid receptor antagonists together with antisense probes directed against each of the four exons of the MOR-1 opioid receptor gene and each of the three exons of the DOR-1, KOR-1, and KOR-3/ORL-1 opioid receptor genes upon feeding elicited by cerebroventricular NPY (0.47 nmol, 2 ug). NPY-induced feeding was dose-dependently decreased and sometimes eliminated following pretreatment with general, μ, δ, and κ 1 opioid receptor antagonists. Moreover, NPY-induced feeding was significantly and markedly reduced by antisense probes directed against exons 1, 2, and 3 of the MOR-1 gene, exons 1 and 2 of the DOR-1 gene, exons 1, 2, and 3 of the KOR-1 gene, and exon 3 of the KOR-3/ORL-1 gene. Thus, whereas the opioid peptides, β-endorphin and dynorphin A 1–17 elicit feeding responses that are respectively more dependent upon μ and κ opioid receptors and their genes, the opioid mediation of NPY-induced feeding appears to involve all three major opioid receptor subtypes in a manner similar to that observed for feeding responses following glucoprivation or lipoprivation.