IN-VIVO LABELING OF DELTA-OPIOID RECEPTORS IN MOUSE-BRAIN BY [3H]BENZYLIDENENALTREXONE, A LIGAND SELECTIVE FOR THE DELTA(1) SUBTYPE

(E)-7-Benzylidenenaltrexone (BNTX) is a selective ligand for the putat ive delta(1) (delta(1)) opioid receptor. To explore the feasibility of labeling delta(1) sites in vivo, we determined the cerebral distribut ion of radioactivity after systemic administration of [H-3]BNTX to CD1 mice. Uptake was highest in striatum and lowest in cerebellum through out the 4 hr time course. Specific radioligand binding, approximated a s the difference in radioactivity concentrations between striatum and cerebellum, peaked at 0.32 percent injected dose/g at 30 min and compr ised a modest 23% of total striatal radioactivity. For seven brain reg ions, radioactivity concentrations correlated with delta site densitie s known from prior in vitro studies (r(S) = 0.79, p = 0.03), and also with the uptake of N1'-([11C]methyl)naltrindole in vivo (r(S) = 0.78, p = 0.04) in mice. Specific binding in striatum, olfactory tubercles a nd cortical regions was saturable by BNTX, and was inhibited stereosel ectively by the optical isomers of naloxone. Naltrindole and naltriben (NTB), delta antagonists, blocked 65 - 99% of [H-3]BNTX specific bind ing at a dosage of 5.0 mu mol/kg, Similar doses of the mu antagonist c yprodime, or the kappa agonist U50,488H, did not inhibit binding. Adju sted for the four-fold greater brain penetration of NTB relative to BN TX, dose-response studies suggested that delta(1) selective BNTX (ED50 = 1.51 mu mol/kg) was 50% more potent than delta(2) selective NTB (ED 50 = 0.56 mu mol/kg) in blocking specific [H-3]BNTX binding in striatu m. In CXBK mice, a strain with functional delta(1) but not delta(2) re ceptors in antinociceptive assays, radioligand uptake and distribution proved similar to that in CD1 mice. In sum, [H-3]BNTX labels murine d elta opioid receptors in vivo with a low extent of specific binding. T he data is consistent with, but not conclusive for, selective labeling of the delta(1) subtype.