Pharmacological and anatomical evidence of selective μ, δ, and χ opioid receptor binding in rat brain

While the distribution of opioid receptors can be differentiated in the rat central nervous system, their precise localization has remained controversial, due, in part, to the previous lack of selective ligands and insensitive assaying conditions. The present study analyzed this issue further by examining the receptor selectivity of [³H]DAGO (Tyr-d-Ala-Gly-MePhe-Gly-ol), [³H]DPDPE (2-d-penicillamine-5-d-penicillamine-enkephalin), [³H]DSLET (Tyr-d-Ser-Gly-Phe-Leu-Thr) and [³H](−)bremazocine, and their suitability in autoradiographically labelling selective subpopulations of opoiod receprtors in rat brain. The results from saturation, competitions, and autoradiographic experiments indicated that the three opioid receptor subtypes can be differentiated in the rat brain and that [³H]-DAGO and [³H]DPDPE selectively labelled μ and δ binding sites, respectively. In contrast, [³H]DSLET was found to be relatively non-selective, and labelled both μ and δ sites. [³H]Bremazocine was similarly non-selective in the absence of μ and δ ligands and labelled all three opioid receptor subtypes. However, in the presence of 100 nM DAGO and DPDPE, concentrations sufficient to saturate the μ and δ sites, [³H]bremazocine did label χ sites selectively. The affinity [³H]bremazocine binding sites showed a unique distribution with relatively dense χ labelling in the hypothalamus and median eminence, areas with extremely low μ and δ binding. These results point to the selectivity, under appropriate conditions, of [³H]DAGO, [³H]DPDPE and [³H]bremazocine and provide evidence for the differential distribution of μ, δ, and χ opioid receptors in rat brain.