[H-3]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 n europsychiatric disorders, "novelty-seeking" behaviors, and effects produce d 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 norm al brain function and in neuropsychiatric disorders. We investigated the au toradiographic distribution of D-4 receptors in non-human primate (Macaca m ulatta) brain (N = 3) with the novel Dq receptor probe [H-3]PNU-101958. Qua ntification of [H-3]PNU-101958 binding sites in 77 brain regions revealed d ense levels of D-4 receptors in several cortical areas, especially in prefr ontal cortex, uncus, hypothalamic median eminence, hippocampal formation, a nd distinct thalamic nuclei, but mere significantly lower in striatum. The results correspond tt ell 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 [H-3]PNU-101958 bin ding sites in non-human primate brain appear to reflect D-4 dopamine recept or 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 psychostimulant s. Synapse 37:232-244, 2000. (C) 2000 Wiley-Liss, Inc.