Autoradiographic localization and quantification of dopamine D2 receptors in normal human brain with [3H]N-n-propylnorapomorphine.

The precise distribution of dopamine receptors has been studied autoradiographically in the normal human brain using [3H]N-n-propylnorapomorphine ([3H]NPA) as a ligand. Preliminary experiments aimed at optimizing the binding assay conditions revealed that preincubation washing of caudate nucleus sections was a prerequisite to obtain a good ratio of specific to non-specific binding. The binding of [3H]NPA to caudate-putamen sections was saturable, stereospecific, reversible, of high affinity (Kd = 0.27-0.35 nM) and occurred at a single population of sites. Competition experiments with various drugs indicated that in the caudate-putamen the specific [3H]NPA binding sites possess the pharmacological features of the dopamine D2 receptor. The highest levels of [3H]NPA binding sites were found in the caudate nucleus, putamen, globus pallidus and nucleus accumbens. There were also intermediate to low concentrations of the 3H-ligand in the hippocampus, the insular and cingular cortices and in the occipito-temporal gyrus, while almost undetectable levels of binding were found in the anterior frontal cortex. Thorough examination of the subregional distribution of [3H]NPA binding sites in the caudate-putamen-pallidum complex revealed heterogeneous patterns of radioactivity. In these brain regions, the distribution of autoradiographic grains was punctate and islands of high and low densities were observed. Moreover, in the caudate nucleus, there was a subtle high lateral to low medial gradient in the topography of the [3H]NPA binding sites and a more pronounced gradient along the rostrocaudal axis; the highest levels of binding being located at the midbody of the nucleus. No gradients of [3H]NPA binding were observed in the putamen. The present data indicate that [3H]NPA is a suitable ligand for accurate autoradiographic labeling of dopamine D2 receptors in human postmortem brain tissue and that dopamine receptors are heterogeneously distributed and topographically organized in patches and gradients in the basal ganglia regions.