In vivo labelling of rat brain dopamine D-2 receptors. Stereoselective blockade by the D-2 antagonist raclopride and its enantiomer of 3H-spiperone, 3H-N,N-propylnorapomorphine and 3H-raclopride binding in the rat brain.

The stereospecific blockade by raclopride and FLB472 (the R enantiomer of raclopride) of the specific in vivo binding of [3H]-spiperone, [3H]-N,N-propylnorapomorphine (NPA) and [3H]-raclopride was studied in seven brain regions (e.g., caudate nucleus, olfactory tubercle, septum, hippocampus, frontal cortex, substantia nigra, pituitary gland) of the male albino rat. The binding of all three ligands was dose-dependently blocked by raclopride and FLB472. The blockade by FLB472 occurred at doses 50-100 times higher than that obtained by raclopride. The maximal blockade by raclopride of [3H]-spiperone binding differed between brain areas. Thus, the largest blockade was obtained in the substantia nigra (95%), septum (90%), caudate nucleus (60%) and olfactory tubercle (60%), while the blockade of [3H]-spiperone binding in the frontal cortex and pituitary gland did not exceed 30% and 50%, respectively. In contrast to [3H]-spiperone, the in vivo binding of [3H]-NPA and [3H]-raclopride was prevented by 90-100% in all brain areas examined. Taken together, the present findings indicate that the in vivo binding of three radioactive ligands to a central dopamine D-2 receptor can be stereoselectively blocked by the enantiomers of raclopride. The findings suggest that, under in vivo conditions, [3H]-raclopride and [3H]-NPA may label a closely related receptor site. However only some of the [3H]-spiperone binding sites may be identical to the [3H]-raclopride binding sites. The findings indicate furthermore that the relative overlap of D-2 sites shared by [3H]-spiperone and [3H]-raclopride may vary between brain regions.