INVIVO LABELING OF THE NEURONAL DOPAMINE UPTAKE COMPLEX IN THE MOUSE STRIATUM BY [H-3] GBR-12783

Various characteristics of the in vivo striatal binding of [H-3]GBR 12783 (1-[2-(diphenylmethoxy)-ethyl]-4-(3-phenyl-1[H-3]-2-propenyl)piperazine), a specific ligand of the neuronal dopamine uptake complex, were determined in mice. Increasing doses of the ligand revealed the saturability of the binding at a single site with half-maximal saturation at a dose of approximately 7 mu-mol/kg and an apparent maximal number of binding sites (B(max)) of 12.8 pmol/mg protein in striatum. Specific binding was prevented by various dopamine uptake blockers, pyrovalerone, GBR 13069, GBR 12783, N-[1-2-benzo(b)thiophenyl)cyclohexyl] piperidine, cocaine, methylphenidate and was inhibited in a stereoselective manner by the enantiomers of nomifensine. Other drugs which are not dopamine uptake blockers either did not modify [H-3]GBR 12783 binding (the diphenylbutylpiperazine derivative flupenthixol) or increased it (the diphenylpiperazine derivative flunarizine or the chemically unrelated compounds fenfluramine and SKF 525A). A close correlation was found between occupancy of the striatal [H-3]GBR 12783 binding site and the stimulant locomotor effect of the drug. A similar specific striatal binding of [H-3]GBR 12783 was evidenced in both NMRI and CD1 strains. It was concluded that [H-3]GBR 12783 administered in vivo provides a measure of the density of dopamine uptake sites in mouse striatum.