DISTRIBUTION OF DOPAMINE D-3 RECEPTOR-EXPRESSING NEURONS IN THE HUMANFOREBRAIN - COMPARISON WITH D-2 RECEPTOR-EXPRESSING NEURONS

The dopamine D-2 and D-3 receptors are members of the D-2 subfamily th at includes the D-2, D-3 and D-4 receptor. In the mt, the D-3 receptor exhibits a distribution restricted to mesolimbic regions with little overlap with the D-2 receptor. Receptor binding and nonisotopic in sit u hybridization were used to study the distribution of the D-3 recepto rs and neurons positive for D-3 mRNA in comparison to the D-2 receptor /mRNA in subcortical regions of the human brain. D-2 binding sites wer e detected in all brain areas studied, with the highest concentration found in the striatum followed by the nucleus accumbens, external segm ent oft he globus pallidus, substantia nigra and ventral tegmental are a, medial preoptic area and tuberomammillary nucleus of the hypothalam us. In most areas the presence of D-2 receptor sites coincided with th e presence of neurons positive for its mRNA. D-3 binding sites and D-3 mRNA positive neurons were most abundant in the limbic striatum and e fferent structures, such as the nucleus accumbens, ventral striatum, s ubstantia nigra, internal segment of the globus pallidus, anteroventra l nucleus of the thalamus, and rostral pars reticulata of the substant ia nigra. One important difference from the rat is that D-3 receptors were virtually absent in the ventral tegmental area. D-3 receptor and D-3 mRNA positive neurons were observed in sensory, hormonal, and asso ciation regions such as the nucleus basalis, anteroventral, mediodorsa l, and geniculate nuclei of the thalamus, mammillary nuclei, the basol ateral basomedial, and cortical nuclei of the amygdala. As revealed by simultaneous labeling for D-3 and D-2 mRNA, D-3 mRNA tons often expre ssed in D-2 mRNA positive neurons. Neurons that solely expressed D-2 m RNA were numerous and regionally widespread, whereas only occasional D -3-positive-D-2-negative cells were observed. The regions of relativel y higher expression of the D-3 receptor and its mRNA appeared linked t hrough functional circuits, but co-expression of D-2 and D-3 mRNA sugg ests a functional convergence in many regions of the signals mediated by the two receptor subtypes. [Neuropsychopharmacology 20:60-80, 1999] (C) 1998 American College of Neuropsychopharmacology. Published by El sevier Science Inc.