Effects of intracerebroventricular β-funaltrexamine on μ and δ opioid receptors in the rat: dichotomy between binding and antinociception

Abstract

The effects of intracerebroventricutar (i.c.v.) β-funaltrexamine (β-FNA) pretreatment at −24 or −6 h were studied on μ and β opioid receptor binding and on antinociception produced by i.c.v. morphine in rats. μ and δ opioid receptor binding in brain membrane preparations was performed with [ 3H][D-Ala 2,MePhe 4Gly-ol 5]enkephalin (DAGO) and [ 3H][D-Pen 2,D-Pen 5]enkephalin (DPDPE) as radiolabeled ligands, respectively. Effects of i.c.v. β-FNA (24 h) on μ, and δ binding depended on dosage. For [ 3h]dago binding, 3 μg, β-FNA did not affect either the K d or B max, whereas 10 μg increased the K dout changing the B max· pretreatment for 24 h did not alter [ 3h]dpdpe binding at 3 μat 10 μ, the K dincreased with no change in the B maxeatment with 10 μg β-FNA for 6 h gave similar results to the 24-h treatment in μ binding, but did not change δ binding. When μ binding was performed on various brain regions, pretreatment with 10 μg β-FNA for 24 h increased the K d in all regions studied (the penaqueductal 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 β-FNA (3 or 10 μg at −24 h), which by itself caused some hyperalgesia, greatly antagonized the antinociceptive effect of morphine (10 μg i.c.v.) in the hot-plate test. Our work with β-FNA has revealed an apparent discrepancy between binding and behavioral results. This dichotomy may, in part, be the result of the limited distribution of β-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 [ 3h]dago binding sites in vitro may not represent functional receptors in vivo.