The dopamine D-2 and D-3 receptors are members of the D-2 subfamily that 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 situ hybridization were used to study the distribution of the D-3 receptors 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 were detected in all brain areas studied, with the highest concentration found in the striatum followed by the nucleus accumbens, external segment oft he globus pallidus, substantia nigra and ventral tegmental area, medial preoptic area and tuberomammillary nucleus of the hypothalamus. In most areas the presence of D-2 receptor sites coincided with the 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 efferent structures, such as the nucleus accumbens, ventral striatum, substantia nigra, internal segment of the globus pallidus, anteroventral nucleus of the thalamus, and rostral pars reticulata of the substantia 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 association regions such as the nucleus basalis, anteroventral, mediodorsal, and geniculate nuclei of the thalamus, mammillary nuclei, the basolateral basomedial, and cortical nuclei of the amygdala. As revealed by simultaneous labeling for D-3 and D-2 mRNA, D-3 mRNA tons often expressed in D-2 mRNA positive neurons. Neurons that solely expressed D-2 mRNA were numerous and regionally widespread, whereas only occasional D-3-positive-D-2-negative cells were observed. The regions of relatively higher expression of the D-3 receptor and its mRNA appeared linked through functional circuits, but co-expression of D-2 and D-3 mRNA suggests 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 Elsevier Science Inc.
