Dopamine D5 receptor immunoreactivity is differentially distributed in GABAergic interneurons and pyramidal cells in the rat medial prefrontal cortex

In the rodent neocortex, the dopamine D5 receptor (D5R) appears to be the predominant subtype of D1-like receptors that are generally considered to play important roles in cognitive functions subserved by the prefrontal cortex (PFC). In this study, to identify the precise localization of D5R in rat PFC, we used a receptor-specific antibody and observed the immunolabeled structures by light and confocal laser scanning microscopies. D5R immunolabeling was found in nearly all neurons, both excitatory and inhibitory neurons. Most of the excitatory neurons showing D5R immunolabeling appear to be pyramidal neurons. In these neurons, D5R immunolabeling was observed throughout somata and dendrites including dendritic spines. In neuropil, almost all of the fiber terminals, represented by synaptophysin immunopositivity, were devoid of D5R. Among inhibitory neuronal subpopulations, we examined parvalbumin-immunopositive neurons (PV neurons), because they form a major subpopulation of fast-spiking neurons. Because parvalbumin immunolabeling enables detection of somata and dendrites as well as axonal profiles, we analyzed the intracellular distribution pattern of D5R immunolabeling. As a result, we found that D5R immunolabeling was mainly in somata and proximal dendrites. The density of intradendritic D5R immunolabeling decreased toward the distal regions. Thus, the distribution pattern of D5R immunolabeling is markedly different between pyramidal neurons and PV neurons. D5R may underlie dopamine modulation of cognitive function in PFC.