Ultrastructural immunocytochemical localization of the dopamine D2 receptor within GABAergic neurons of the rat striatum.

Classical antipsychotics, which block dopamine (DA) D2 receptors, showing 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 D2 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 D2 receptor immunoreactivity (D2-IR) 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 are dually labeled with D2-IR and GABA-IR. Neurons axon terminals in each region also contained one or both markers. However, there were notable regional differences in the immunolabeling patterns. In the CPn, D2-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, D2-IR was detected with similar frequency in terminals and dendrites/spines, but more terminals co-localized D2-IR and GABA-IR in this region compared with the CPn. These results provide the first ultrastructural evidence for direct D2-mediated effects of DA on striatal GABAergic neurons. They further suggest that modulation of GABAergic neurons by DA acting at D2 receptors may be relatively more postsynaptic in the CPn, but more presynaptic in the Acb shell.