Dynorphin A1-17-induced feeding: Pharmacological characterization using selective opioid antagonists and antisense probes in rats

Robert M. Silva, Henya C. Grossman, Maria M. Hadjimarkou, Grace C. Rossi, Gavril W. Pasternak, Richard J. Bodnar

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)513-518
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume301
Issue number2
DOIs
Publication statusPublished - 2002

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