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Journal of Neuroscience, Vol 15, 7821-7836, Copyright © 1995 by Society for Neuroscience
Regional, cellular, and subcellular variations in the distribution of D1 and D5 dopamine receptors in primate brain
C Bergson, L Mrzljak, JF Smiley, M Pappy, R Levenson and PS Goldman-Rakic
Department of Pharmacology, Pennsylvania State College of Medicine, USA.
The pathways governing signal transduction in the mesocortical and
nigrostriatal 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 related D1
and D5 subtypes of dopamine receptors in the cerebral cortex and selected
subcortical structures of rhesus monkey using subtype specific antibodies.
The distribution of D1 and D5 receptors was highly differentiated in
subcortical structures. In the neostriatum, both D1 and to a lesser extent
D5 antibodies labeled medium spiny neurons, while only D5 antibodies
labeled the large aspiny neurons typical of cholinergic interneurons. In
the caudate nucleus, D1 labeling was concentrated in the spines and shafts
of projection neurons, whereas D5 antibodies predominantly labeled the
shafts, and less commonly, the spines of these cells. The D1 receptor was
abundantly expressed in the neuropil of the substantia nigra pars
reticulata while the D5 antibodies labeled only a few scattered cell bodies
in this structure. Conversely, D5 antibodies labeled cholinergic neurons in
the basal forebrain more intensely than D1 antibodies. Within the cerebral
cortex and hippocampus, D1 and D5 antibody labeling was prominent in
pyramidal cells. Double-label experiments revealed that the two receptors
were frequently coexpressed in neurons of both structures.
Ultrastructurally, D1 receptors were especially prominent in dendritic
spines whereas dendritic shafts were more prominently labeled by the D5
receptor. The anatomical segregation of the D1 and D5 receptors at the
subcellular level in cerebral cortex and at the cellular level in
subcortical areas suggest that these closely related receptors may be
preferentially associated with different circuit elements and may play
distinct regulatory roles in synaptic transmission.
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