NPY-induced feeding: Pharmacological characterization using selective opioid antagonists and antisense probes in rats Journal Article


Authors: Israel, Y.; Kandov, Y.; Khaimova, E.; Kest, A.; Lewis, S. R.; Pasternak, G. W.; Pan, Y. X.; Rossi, G. C.; Bodnar, R. J.
Article Title: NPY-induced feeding: Pharmacological characterization using selective opioid antagonists and antisense probes in rats
Abstract: 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 κ1 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 κ1 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 A1-17 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. © 2005 Elsevier Inc. All rights reserved.
Keywords: controlled study; exon; dose response; nonhuman; animals; animal experiment; feeding behavior; drug effect; drug mechanism; rat; rats; rats, sprague-dawley; mu opiate receptor; oligodeoxyribonucleotides, antisense; beta funaltrexamine; naltrindole; naltrexone; behavior, animal; neuropeptide y; delta opiate receptor; opiate antagonist; kappa opiate receptor; antisense oligodeoxynucleotide; narcotic antagonists; receptors, opioid; β-funaltrexamine; δ opioid receptor; κ opioid receptor; μ opioid receptor; nor-binaltorphamine; norbinaltorphimine; nucleic acid probe; appetite regulation
Journal Title: Peptides
Volume: 26
Issue: 7
ISSN: 0196-9781
Publisher: Elsevier Science Inc.  
Date Published: 2005-07-01
Start Page: 1167
End Page: 1175
Language: English
DOI: 10.1016/j.peptides.2005.01.017
PUBMED: 15949635
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 13" - "Export Date: 24 October 2012" - "CODEN: PEPTD" - "Source: Scopus"
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  1. Yingxian Pan
    132 Pan
  2. Gavril W Pasternak
    414 Pasternak