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

Y. Israel, Y. Kandov, E. Khaimova, A. Kest, S. R. Lewis, G. W. Pasternak, Y. X. Pan, G. C. Rossi, R. J. Bodnar

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1167-1175
Number of pages9
JournalPeptides
Volume26
Issue number7
DOIs
StatePublished - Jul 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience

Keywords

  • Naltrexone
  • Naltrindole
  • Nor-binaltorphamine
  • β-Funaltrexamine
  • δ opioid receptor
  • κ opioid receptor
  • μ opioid receptor

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