Ultrastructural immunocytochemical localization of the dopamine D-2 receptor within GABAergic neurons of the rat striatum

Classical antipsychotics, which block dopamine (DA) D-2 receptors, show intrastriatal variation in their effectiveness in modulating GABAergic function. To determine the cellular basis for such differences, we examined the electron microscopic immunocytochemical labeling of D-2 receptors and GABA in the dorsolateral caudate-putamen (CPn) and the nucleus accumbens (Acb) shell. In both regions, peroxidase reaction product and gold-silver deposits representing D-2 receptor immunoreactivity (D-2-LR) and GABA immunoreactivity (GABA-IR), respectively, were detected in dendrites and perikarya having characteristics of either spiny projection neurons or aspiny interneurons. Some perikarya in both regions were dually labeled with D-2-IR and GABA-IR. Numerous axon terminals in each region also contained one or both markers. However, there were notable regional differences in the immunolabeling patterns. In the CPn, D-2-IR was more commonly seen in dendrites/spines than in axon terminals, and proportionally more dendrites were dually labeled than in the Acb. In the Acb shell, D-2-LR was detected with similar frequency in terminals and dendrites/spines, but more terminals co-localized D-2-IR and GABA-IR in this region compared with the CPn. These results provide the first ultrastructural evidence for direct D-2-mediated effects of DA on striatal GABAergic neurons. They further suggest that modulation of GABAergic neurons by DA acting at D-2 receptors may be relatively more postsynaptic in the CPn, but more presynaptic in the Acb shell.