REGIONAL, CELLULAR, AND SUBCELLULAR VARIATIONS IN THE DISTRIBUTION OFD-1 AND D-2 DOPAMINE-RECEPTORS IN PRIMATE BRAIN

The pathways governing signal transduction in the mesocortical and nig rostriatal dopamine systems of the brain are of central importance in a variety of drug actions and neurological diseases. We have analyzed the regional, cellular, and subcellular distribution of the closely re lated D-1 and D-5 subtypes of dopamine receptors in the cerebral corte x and selected subcortical structures of rhesus monkey using subtype s pecific antibodies. The distribution of D-1 and D-5 receptors was high ly differentiated in subcortical structures. In the neostriatum, both D-1 and to a lesser extent D-5 antibodies labeled medium spiny neurons , while only D-5 antibodies labeled the large aspiny neurons typical o f cholinergic interneurons. In the caudate nucleus, D-1 labeling was c oncentrated in the spines and shafts of projection neurons, whereas D- 5 antibodies predominantly labeled the shafts, and less commonly, the spines of these cells. The D-1 receptor was abundantly expressed in th e neuropil of the substantia nigra pars reticulata while the D-5 antib odies labeled only a few scattered cell bodies in this structure. Conv ersely, D-5 antibodies labeled cholinergic neurons in the basal forebr ain more intensely than D-1 antibodies. Within the cerebral cortex and hippocampus, D-1 and D-5 antibody labeling was prominent in pyramidal cells. Double-label experiments revealed that the two receptors were frequently coexpressed in neurons of both structures. Ultrastructurall y, D-1 receptors were especially prominent in dendritic spines whereas dendritic shafts were more prominently labeled by the D-5 receptor. T he anatomical segregation of the D-1 and D-5 receptors at the subcellu lar level in cerebral cortex and at the cellular level in subcortical areas suggest that these closely related receptors may be preferential ly associated with different circuit elements and may play distinct re gulatory roles in synaptic transmission.