EFFECTS OF INTRACEREBROVENTRICULAR BETA-FUNALTREXAMINE ON MU AND-DELTA OPIOID RECEPTORS IN THE RAT - DICHOTOMY BETWEEN BINDING AND ANTINOCICEPTION

The effects of intracerebroventricular (i.c.v.) beta-funaltrexamine (beta-FNA) pretreatment at -24 or -6 h were studied on mu and delta-opioid receptor binding and on antinociception produced by i.c.v. morphine in rats. mu and delta-opioid receptor binding in brain membrane preparations was performed with [H-3][D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO) and [H-3][D-Pen2,D-Pen5]enkephalin (DPDPE) as radiolabeled ligands, respectively. Effects of i.c.v. beta-FNA (24 h) on mu and delta-binding depended on dosage. For [H-3]DAGO binding, 3-mu-g beta-FNA did not affect either the K(d) or B(max), whereas 10-mu-g increased the K(d) without changing the B(max). Beta-FNA pretreatment for 24 h did not alter [H-3]DPDPE binding at 3-mu-g; at 10-mu-g, the K(d) was increased with no change in the B(max). Pretreatment with 10-mu-g beta-FNA for 6 h gave similar results to the 24-h treatment in mu-binding, but did not change delta-binding. When mu-binding was performed on various brain regions, pretreatment with 10-mu-g beta-FNA for 24 h increased the K(d) in all regions studied (the periaqueductal gray, thalamus, striatum and cortex). However, this pretreatment decreased the B(max) only in the periaqueductal gray (by 22%) and cortex (by 14%). Pretreatment of rats with beta-FNA (3 or 10-mu-g at -24 h), which by itself caused some hyperalgesia, greatly antagonized the antinociceptive effect of morphine (10-mu-g i.c.v.) in the hot-plate test. Our work with beta-FNA has revealed an apparent discrepancy between binding and behavioral results. This dichotomy may, in part, be the result of the limited distribution of beta-FNA to the periventricular area. It may also be due to the presence of uncoupled receptors and/or may be related to the finding that high affinity [H-3]DAGO binding sites in vitro may not represent functional receptors in vivo.