Differential perikaryal localization in rats of D1 and D2 dopamine receptors on striatal projection neuron types identified by retrograde labeling.

The localization of D1 and D2 dopamine receptors to striatal projection neuron types has been controversial, with some data favoring segregation of D1 to direct pathway neurons (substance P-containing) and D2 to indirect pathway neurons (enkephalinergic), and others reporting significant colocalization of D1 and D2 on individual projection neuron types. In the present study, we used subtype-specific antibodies against D1 and D2 and confocal laser scanning microscopy to determine their perikaryal localization in striatum in general, and in direct and indirect pathway neuron perikarya defined by retrograde labeling in particular. We found that D1 in rat was detectable on 49.5% of NeuN-immunolabeled striatal perikarya, and D2 on 61.6% of NeuN-immunolabeled perikarya, implying that at least 15-20% of D1+ neurons must possess D2 and vice versa. Secondly, we retrogradely labeled neuronal perikarya from the external globus pallidus (GPe), internal globus pallidus (GPi) or substantia nigra with rhodamine dextran amine 3 kDa (RDA3k). We found that 92% of perikarya labeled from nigra and 96% of perikarya labeled from GPi immunolabeled for D1, but only 23% of perikarya labeled from GPe immunolabeled for D1. Since direct pathway neurons (striato-nigral and striato-GPi) have a collateral projection to GPe, it is possible that many of the D1+ striatal perikarya retrogradely labeled from GPe were direct pathway neurons. About 96% of perikarya retrogradely labeled from GPe were immunolabeled for D2, while about 40% of those retrogradely labeled from GPi and 44% of those retrogradely labeled from nigra immunolabeled for D2. These findings suggest that: (1) while many striato-GPi/SN neurons possess D1 and D2, the majority mainly or exclusively possess D1 and (2) the vast majority of striato-GPe neurons mainly or exclusively possess D2.