[(3)H]PNU-101958, a D(4) dopamine receptor probe, accumulates in prefrontal cortex and hippocampus of non-human primate brain

The D(4) Dopamine Receptor has been investigated for its potential role in neuropsychiatric disorders, "novelty-seeking" behaviors, and effects produced by some psychostimulants. An accurate map of D(4) distribution and density in brain is essential to clarify the role of this receptor subtype in normal brain function and in neuropsychiatric disorders. We investigated the autoradiographic distribution of D(4) receptors in non-human primate (Macaca mulatta) brain (N = 3) with the novel D(4) receptor probe [(3)H]PNU-101958. Quantification of [(3)H]PNU-101958 binding sites in 77 brain regions revealed dense levels of D(4) receptors in several cortical areas, especially in prefrontal cortex, uncus, hypothalamic median eminence, hippocampal formation, and distinct thalamic nuclei, but were significantly lower in striatum. The results correspond well with previous reports of brain distribution of D(4) receptors using other radiolabeled probes, and of D(4) mRNA localization (with some exceptions). Overall, this study reveals that [(3)H]PNU-101958 binding sites in non-human primate brain appear to reflect D(4) Dopamine Receptor distribution. The significance of a dense localization of D(4) receptors in prefrontal cortex and hippocampus, and broad distribution in other brain areas, allows for investigation of the relationship of these receptors to specific neuropsychiatric disorders and effects produced by psychostimulants.