LOCALIZATION OF D(1) AND D(2) DOPAMINE-RECEPTORS IN BRAIN WITH SUBTYPE-SPECIFIC ANTIBODIES

Five or more dopamine receptor genes are expressed in brain. However, the pharmacological similarities of the encoded D1-D5 receptors have h indered studies of the localization and functions of the subtypes. To better understand the roles of the individual receptors, antibodies we re raised against recombinant D1 and D2 proteins and were shown to bin d to the receptor subtypes specifically in Western blot and immunoprec ipitation studies. Each antibody reacted selectively with the respecti ve receptor protein expressed both in cells transfected with the cDNAs and in brain. By immunocytochemistry, D1 and D2 had similar regional distributions in rat, monkey, and human brain, with the most intense s taining in striatum, olfactory bulb, and substantia nigra. Within each region, however, the precise distributions of each subtype were disti nct and often complementary. D1 and D2 were differentially enriched in striatal patch and matrix compartments, in selective layers of the ol factory bulb, and in either substantia nigra pan compacta or reticulat a. Electron microscopy demonstrated that D1 and D2 also had highly sel ective subcellular distributions. In the rat neostriatum, the majority of D1 and D2 immunoreactivity was localized in postsynaptic sites in subsets of spiny dendrites and spine heads in rat neostriatum. Presyna ptic D1 and D2 receptors were also observed, indicating both subtypes may regulate neurotransmitter release. D1 was also Present in axon ter minals in the substantia nigra. These results provide a morphological substrate for understanding the pre- and postsynaptic functions of the genetically defined D1 and D2 receptors in discrete neuronal circuits in mammalian brain.