Reduction by central beta-funaltrexamine of food intake in rats under freely-feeding, deprivation and glucoprivic conditions.

The present study evaluated the central effects of beta-funaltrexamine (B-FNA), a non-equilibrium antagonist of mu-opioid receptors and a reversible agonist of kappa-opioid receptors upon food intake in rats under freely-feeding, deprivation and glucoprivic conditions. B-FNA elicited distinct short-term and long-term actions, consistent with binding studies demonstrating its reversible kappa agonist actions and its irreversible mu receptor blockade. Whereas B-FNA (1-20 micrograms, i.c.v.) significantly stimulated free feeding for up to 6 h, B-FNA (10-20 micrograms) significantly inhibited (35-41%) free feeding at 24, 48 and 72 h after injection, a pattern temporally similar to its biochemical opioid effects. Pretreatment (24 h) with B-FNA (10-20 micrograms) significantly inhibited (33-49%) the increased intake following 24 h of food deprivation. Pretreatment (24 h) with B-FNA (10-20 micrograms) also significantly inhibited (75-100%) the increased glucoprivic intake induced by 2-deoxy-D-glucose. The short-term stimulation of food intake by central B-FNA was antagonized by the selective kappa antagonist, nor-binaltorphamine, but was unaffected by pretreatment 24 h earlier with the mu antagonist, B-FNA. Significant reductions in striatal (89%) and hypothalamic (46%) mu-opioid binding occurred in rats pretreated (24 h) with B-FNA; the low levels of delta binding in these structures precluded interpretation of B-FNA effects. These data indicate the importance of the mu-opioid receptor in the modulation of different forms of feeding behavior, and underscores the ability of selective opioid antagonists to delineate precise functional roles for different opioid receptor subtypes.