Phenotypical characterization of neurons expressing the dopamine D3 receptor in the rat brain

Abstract We have established the cellular distribution of the dopamine D 3 receptor using tritiated 7-hydroxy- N-N -di-n-propyl-2-aminotetralin and a complementary RNA probe to visualize autoradiographically the protein in binding studies and the gene transcripts by in situ hybridization, respectively. Studies with these two markers confirm the restricted expression of the D 3 receptor in few brain areas, i.e. mainly the ventral striatal complex, the substantia nigra-ventral tegmental area and the cerebellum. In nucleus accumbens, the D 3 receptor was mainly expressed in medium-sized neurons of the rostral pole and ventromedial shell subdivisions, but not of the core or septal pole, i.e. accumbal subdivisions expressing the D 2 receptor. In the ventromedial shell, about 60% of the D 3 receptor-expressing neurons were neurotensin neurons, presumably projecting to the ventral pallidum. In the islands of Calleja, both D 3 receptor binding and messenger RNA were abundant in the entire population of granule cells. These cells are known to make sparse contacts with dopaminergic axons and also to express the D 1 receptor. In the mesencephalon, low levels of D 3 messenger RNA were detected in few dopamine neurons of substantia nigra pars lateralis and ventral tegmental area. In addition, some D 3 receptor binding but not messenger RNA was detected in medial substantia nigra and lateral ventral tegmental area, where the receptor is presumably located presynaptically on afferents. In the archicerebellum, Purkinje cell perikarya in lobules 9 and 10 expressed the D 3 receptor messenger RNA, whereas binding sites were found in the molecular layer, where corresponding dendrites but no known dopaminergic projection from mesencephalon are found. The occurrence of D 3 receptor gene expression in some brain areas receiving low dopamine innervation supports the hypothesis that this receptor may mediate non-synaptic actions of dopamine.