Dynorphin A1–17-Induced Feeding: Pharmacological Characterization Using Selective Opioid Antagonists and Antisense Probes in Rats
- Robert M. Silva1,
- Henya C. Grossman1,
- Maria M. Hadjimarkou1,
- Grace C. Rossi2,3,
- Gavril W. Pasternak2 and
- Richard J. Bodnar1
- 1Department of Psychology and Neuropsychology Doctoral Sub-Program, City University of New York, Flushing, New York (R.M.S., H.C.G., M.M.H., R.J.B.); 2The George C. Cotzias Laboratory of Neuro-Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (G.C.R., G.W.P.); and 3Department of Psychology, CW Post College, Long Island University, Brookville, New York (G.C.R.)
- Dr. R. J. Bodnar, Department of Psychology, Queens College, City University of New York, 65-30 Kissena Blvd., Flushing, NY 11367. E-mail:richard_bodnar{at}qc.edu
Abstract
Ventricular administration of the opioid dynorphin A1–17induces 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 μ-antagonist 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 reducing 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.
Footnotes
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This research was supported in part from National Science Foundation Grant IBN98-16699 (to R.J.B.), National Institute of Drug Abuse Grants DA07274 (to G.W.P.), DA00220 (to G.W.P.), and DA00310 (to G.C.R.), City University of New York Science Fellowships (to R.M.S. and M.M.H.), and Queens College Howard Hughes Medical Institute Grant Summer Program for Undergraduate Research (to H.C.G.).
- Abbreviations:
- AS ODN
- antisense oligodeoxynucleotide
- MOR-1
- μ-opioid receptor clone
- DOR-1
- δ-opioid receptor clone
- KOR-1
- κ-opioid receptor clone
- KOR-3/ORL-1
- κ3-like opioid receptor clone
- Ntx
- naltrexone
- βFNA
- β-funaltrexamine
- NBNI
- nor-binaltorphamine
- MS ODN
- missense oligodeoxynucleotide
- U50488H
- trans-(±)-3,4-dichloro-N-methyl-N-(2-[1-pyrro-lidnyl]cyclohexyl)benzeneacetamide methane solfonate salt
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- Received August 31, 2001.
- Accepted January 10, 2001.
- The American Society for Pharmacology and Experimental Therapeutics
