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Vol. 297, Issue 2, 590-596, May 2001

beta -Endorphin-Induced Feeding: Pharmacological Characterization Using Selective Opioid Antagonists and Antisense Probes in Rats

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

Department of Psychology and Neuropsychology Doctoral Sub-Program, Queens College, City University of New York, Flushing, New York (R.M.S., M.M.H., R.J.B.); Department of Psychology, CW Post College, Long Island University, Brookville, New York (G.C.R.); and The George C. Cotzias Laboratory of Neuro-Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (G.C.R., G.W.P.)

Ventricular administration of the opioid beta END induces feeding in rats. Since its pharmacological characterization has not been fully identified, the present study examined whether equimolar doses of general and selective opioid antagonists as well as AS ODN opioid probes altered spontaneous daytime feeding over a 4-h time course elicited by beta END. beta END-induced feeding was significantly reduced by moderate (20-40-nmol, i.c.v.) doses of general (naltrexone) opioid antagonists, and lower (0.5-40-nmol) doses of selective µ (beta -funaltrexamine)-antagonists. Correspondingly, AS ODN probes directed against either exons 1, 3, or 4, but not exon 2, of the µ-opioid receptor clone reduced beta END-induced feeding; a missense ODN control probe was ineffective. The delta -antagonist Nti (20-40 nmol) reduced beta END-induced feeding to a lesser degree, and AS ODN probes targeting exon 1, but not 2 or 3, of the delta -opioid receptor clone significantly reduced beta END-induced feeding. Although the selective kappa 1-receptor antagonist NBNI (20-40 nmol) significantly reduced beta END-induced feeding, this response was not altered by AS ODN probes directed against either exons 1, 2, or 3 of either the KOR-1 clone or the kappa 3-like opioid receptor clone. These converging antagonist and AS ODN data firmly implicate the µ-opioid receptor in the mediation of beta END-induced feeding. The relative lack of convergence between the lesser effectiveness of Nti and NBNI in reducing beta END-induced feeding, and the lack of effectiveness of their corresponding AS ODN probes suggest that delta - and kappa -receptors play a minimal role in the mediation of this response.

0022-3565/01/2972-0590$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2001 by The American Society for Pharmacology and Experimental Therapeutics


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