Dynorphin A(1-17)-induced feeding: pharmacological characterization using selective opioid antagonists and antisense probes in rats.
Ventricular administration of the opioid dynorphin A(1-17) 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 kappa(1)-opioid antagonist nor-binaltorphamine. Correspondingly, AS ODN probes directed against either exons 1 and 2, but not 3 of the kappa-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 kappa(3)-like opioid receptor clone (KOR-3/ORL-1) also attenuated dynorphin-induced feeding. Although the selective mu-antagonist beta-funaltrexamine (20-80 nmol) reduced dynorphin-induced feeding, an AS ODN probe directed only against exon 1 of the mu-opioid receptor clone was transiently effective. Neither general (naltrexone, 80 nmol) nor delta (naltrindole, 80 nmol)-selective opioid antagonists were particularly effective in reducing dynorphin-induced feeding, and an AS ODN probe targeting the individual exons of the delta-opioid receptor clone failed to significantly reduce dynorphin-induced feeding. These converging antagonist and AS ODN data firmly implicate the kappa(1)-opioid receptor and the KOR-1 and KOR-3/ORL-1 opioid receptor genes in the mediation of dynorphin-induced feeding.
Silva
Robert M
RM
Department of Psychology and Neuropsychology Doctoral Sub-Program, City University of New York, Flushing, New York 11367, USA.
Grossman
Henya C
HC
Hadjimarkou
Maria M
MM
Rossi
Grace C
GC
Pasternak
Gavril W
GW
Bodnar
Richard J
RJ
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004399:Dynorphins / Q000494:pharmacology*; D005247:Feeding Behavior / Q000187:drug effects*; D008297:Male; D023421:Models, Animal; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000378:metabolism; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000378:metabolism
D009292:Narcotic Antagonists; D016376:Oligonucleotides, Antisense; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C051844:norbinaltorphimine; D009271:Naltrexone; C024524:beta-funaltrexamine; D004399:Dynorphins; C055382:naltrindole