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BEHAVIORAL PHARMACOLOGY

Opioid Receptor Involvement in Food Deprivation-Induced Feeding: Evaluation of Selective Antagonist and Antisense Oligodeoxynucleotide Probe Effects in Mice and Rats

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.)

Central administration of general and selective opioid receptor subtype antagonists in the rat has revealed a substantial role for µ, a moderate role for , and a minimal role for receptors in the mediation of deprivation-induced feeding. Antisense probes directed against the opioid receptor (KOP), nociceptin opioid receptor (NOP), and opioid receptor (DOP) genes in rats result in reductions similar to and 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 opioid antagonists. In contrast, mice, but not rats, displayed reductions in deprivation-induced intake following antagonism as well as DOP antisense probes, suggesting a species-specific role for the receptor. Antisense probes directed against the KOP and NOP genes also reduced deprivation-induced intake in mice in a manner similar to 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.

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

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