Cellular colocalization of dopamine D1 and D2 receptors in rat medial prefrontal cortex

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Abstract
In a recent study in rat medial prefrontal cortex (mPFC), a fluorescently coupled, high‐affinity ligand for the D1 receptor subtype was localized to nonpyramidal neurons, while a ligand selective for the D2 subtype was found on neurons with a size distribution overlapping with both small pyramidal and large nonpyramidal cells. These observations raised the possibility that a subpopulation of cortical neurons with an intermediate size range may coexpress both the D1 and D2 receptor subtypes. In the present study, the D1 and D2 receptor subtypes have been simultaneously localized in layer VI of rat mPFC using 20 nM SCH 23390‐Bodipy and 20 nM N‐(p‐aminophenethyl) spiperone‐Texas red, respectively, in the presence of 100 nM mianserin (5‐HT2 receptor antagonist). The localization of receptor binding fluorescence was assessed in paired images using fluoresceiN isothiocyanate (FITC) and rhodamine dichroic filters for the D1 and D2 subtypes, respectively. Under the conditions employed here, most cell bodies showed either Dl‐like or D2‐like receptor binding fluorescence, while a colocalization of both fluoroprobes was observed on only 25% of the labeled cells. When the size of each single‐labeled cell body was measured using the respective FITC (D1‐probe) and rhodamine (D2‐probe) epifluorescence filters, the distribution of cells showing only D1‐like receptor binding fluorescence was similar to nonpyramidal neurons (68.6 ± 1.8 μm2), while that for cells showing only D2‐like receptor binding fluorescence was similar to that of both large interneurons and small pyramidal cells (106.9 ± 2.4 μm2). Cells showing both D1‐ and D2‐like receptor binding fluorescence were found to overlap in size only with nonpyramidal cells when either fluorescent filter was used. These findings are consistent with the hypothesis that the D1 and D2 receptor subtypes are most often found on different populations of neurons in mPFC, although approximately 25% of all such cells appear to be nonpyramidal neurons having both D1 and D2 receptor binding activity. These findings suggest that the dopamine projections to rat cortex probably engage in a complex interplay with intrinsic cortical neurons and their respective neurotransmitter systems.