Dynorphin A1-17-induced feeding: Pharmacological characterization using selective opioid antagonists and antisense probes in rats Journal Article
| Authors: | Silva, R. M.; Grossman, H. C.; Hadjimarkou, M. M.; Rossi, G. C.; Pasternak, G. W.; Bodnar, R. J. |
| Article Title: | Dynorphin A1-17-induced feeding: Pharmacological characterization using selective opioid antagonists and antisense probes in rats |
| Abstract: | Ventricular administration of the opioid dynorphin A1-17 induces feeding in rats. Because its pharmacological characterization has not been fully identified, the present study examined whether a dose-response range of general and selective opioid antagonists as well as antisense oligodeoxynucleotide (AS ODN) opioid probes altered daytime feeding over a 4-h time course elicited by dynorphin. Dynorphin-induced feeding was significantly reduced by a wide range of doses (5-80 nmol i.c.v.) of the selective κ1-opioid antagonist nor-binaltorphamine. Correspondingly, AS ODN probes directed against either exons 1 and 2, but not 3 of the κ-opioid receptor clone (KOR-1) reduced dynorphin-induced feeding, whereas a missense oligodeoxynucleotide control probe was ineffective. Furthermore, AS ODN probes directed against either exons 1 or 2, but not 3 of the κ3-like opioid receptor clone (KOR-3/ORL-1) also attenuated dynorphin-induced feeding. Although the selective μantagonist β-funaltrexamine (20-80 nmol) reduced dynorphin-induced feeding, an AS ODN probe directed only against exon 1 of the μ-opioid receptor clone was transiently effective. Neither general (naltrexone, 80 nmol) nor δ (naltrindole, 80 nmol)-selective opioid antagonists were particularly effective in reducting dynorphin-induced feeding, and an AS ODN probe targeting the individual exons of the δ-opioid receptor clone failed to significantly reduce dynorphin-induced feeding. These converging antagonist and AS ODN data firmly implicate the κ1-opioid receptor and the KOR-1 and KOR-3/ORL-1 opioid receptor genes in the mediation of dynorphin-induced feeding. |
| Keywords: | controlled study; unclassified drug; exon; missense mutation; dose response; nonhuman; animals; animal experiment; feeding behavior; dose-response relationship, drug; drug selectivity; food intake; models, animal; rat; rats; rats, sprague-dawley; time series analysis; mu opiate receptor; mu opiate receptor antagonist; receptors, opioid, mu; drug interactions; oligodeoxynucleotide; beta funaltrexamine; naltrindole; naltrexone; oligonucleotides, antisense; delta opiate receptor; opiate antagonist; receptors, opioid, delta; animal behavior; circadian rhythm; dynorphin a; kappa opiate receptor; antisense oligodeoxynucleotide; narcotic antagonists; receptors, opioid; norbinaltorphimine; male; priority journal; article; receptors, opioid, kappa; delta opiate receptor antagonist; kappa opiate receptor antagonist; kappa 1 opiate receptor; kappa 3 opiate receptor; dynorphins |
| Journal Title: | Journal of Pharmacology and Experimental Therapeutics |
| Volume: | 301 |
| Issue: | 2 |
| ISSN: | 0022-3565 |
| Publisher: | American Society for Pharmacology and Experimental Therapeutics |
| Date Published: | 2002-05-01 |
| Start Page: | 513 |
| End Page: | 518 |
| Language: | English |
| DOI: | 10.1124/jpet.301.2.513 |
| PUBMED: | 11961051 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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