Opioid Receptor Involvement in Food Deprivation-Induced Feeding: Evaluation of Selective Antagonist and Antisense Oligodeoxynucleotide Probe Effects in Mice and Rats
- M. M. Hadjimarkou,
- A. Singh,
- Y. Kandov,
- Y. Israel,
- Y.-X. Pan,
- G. C. Rossi,
- G. W. Pasternak and
- R. J. Bodnar
- Department of Psychology and Neuropsychology Doctoral Sub-Program, Queens College, City University of New York, Flushing, New York (M.M.H., A.S., Y.K., Y.I., R.J.B.); Laboratory of Molecular Neuropharmacology, Memorial Sloan-Kettering Cancer Center, New York, New York (Y.-X.P., G.C.R., G.W.P.); and Department of Psychology, C. W. Post College, Long Island University, Brookville, New York (G.C.R.)
- Address correspondence to:
Dr. Richard J. Bodnar, Department of Psychology, Queens College, CUNY, 65-30 Kissena Blvd., Flushing, NY 11367. E-mail: richard_bodnar{at}qc.edu
Abstract
Central administration of general and selective opioid receptor subtype antagonists in the rat has revealed a substantial role for μ, a moderate role for κ, and a minimal role for δ receptors in the mediation of deprivation-induced feeding. Antisense probes directed against the κ opioid receptor (KOP), nociceptin opioid receptor (NOP), and δ opioid receptor (DOP) genes in rats result in reductions similar to κ and δ antagonists, whereas antisense probes directed against the μ opioid receptor (MOP) gene produced modest reductions relative to μ antagonists, suggesting that isoforms of the MOP gene may mediate deprivation-induced feeding. Since these isoforms were initially identified in mice, the present study compared the effects of general and selective opioid receptor antagonists on deprivation-induced feeding in rats and mice and antisense probes directed against exons of the MOP, DOP, KOP, and NOP genes on deprivation-induced feeding in the mouse. Food-deprived (12 and 24 h) rats and mice displayed similar profiles of reductions in deprivation-induced feeding following general, μ, and κ opioid antagonists. In contrast, mice, but not rats, displayed reductions in deprivation-induced intake following δ antagonism as well as DOP antisense probes, suggesting a species-specific role for the δ receptor. Antisense probes directed against the KOP and NOP genes also reduced deprivation-induced intake in mice in a manner similar to κ antagonism. However, the significant reductions in deprivation-induced feeding following antisense probes directed against either exons 2, 4, 7, 8, or 13 of the MOP gene were modest compared with μ antagonism, suggesting a role for multiple μ-mediated mechanisms.
Footnotes
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This research was supported in part by a National Science Foundation Grant (IBN98-16699 to R.J.B.), National Institute of Drug Abuse Grants (DA07242 and DA00220 to G.W.P., DA00310 to G.C.R., and DA13997 to Y.-X.P.), Professional Staff Congress-City University of New York (CUNY) Grants (63278, 64298, and 65285 to R.J.B.), CUNY Collaborative Grant (80209 to R.J.B.), CUNY Graduate Science Fellowship (M.M.H.), and CUNY Honors College (Y.I.).
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.104.071761.
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ABBREVIATIONS: AS ODN, antisense oligodeoxynucleotide(s); MOP, μ opioid receptor; MOR-1, μ opioid receptor clone; DOP, δ opioid receptor; DOR-1, δ opioid receptor clone; KOP, κ opioid receptor; KOR-1, κ opioid receptor clone; NOP, nociceptin opioid receptor; KOR-3/ORL-1, κ3/orphan receptor-like opioid receptor clone; 2DG, 2-deoxy-d-glucose; DAMGO, [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin; M6G, morphine-6-glucuronide; βFNA, β-funaltrexamine; NTI, naltrindole; NBNI, nor-binaltorphamine.
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- Received June 21, 2004.
- Accepted August 27, 2004.
- The American Society for Pharmacology and Experimental Therapeutics
