Subcellular localization of the dopamine D 2 receptor and coexistence with the calcium‐binding protein neuronal calcium sensor‐1 in the primate prefrontal cortex

Structures of the cerebral cortex expressing the D2 dopamine receptor subtype (D 2 ) are important sites of action of antipsychotic drugs. It has also been repeatedly suggested that the prefrontal cortex plays a significant role in neuropsychiatric disorders, including schizophrenia. Here, by using single and double immunohistochemical techniques with electron microscopy, we investigated in the primate prefrontal cortex the ultrastructural localization of D 2 and we compared it with that of the neuronal calcium sensor‐1 (NCS‐1), a neuron‐specific calcium‐binding and D 2 ‐interacting protein. D 2 immunoreactivity, revealed with preembedding immunoperoxidase in single labeling and with preembedding immunogold for double labeling, was localized in cell bodies with ultrastructural characteristics of both neurons and astroglia. D 2 was localized in pre‐ and postsynaptic structures, including spines and dendrites, and in both excitatory‐ and inhibitory‐like axon terminals. Immunogold labeling revealed peri‐ and extrasynaptic localization of D 2 in postsynaptic structures, whereas extrasynaptic labeling was typically found in boutons. NSC‐1 immunoreactivity was abundant in pre‐ and postsynaptic structures, in which it was also colocalized with D 2 . With the present strategy (that has high resolution but relatively limited sensitivity), NSC‐1 was observed in about 10% of the D 2 ‐immunopositive spines and in a lower proportion of D 2 ‐immunopositive dendrites and boutons. The data demonstrate the localization of D 2 in pre‐ and postsynaptic as well as extra‐ and perisynaptic structures of the primate prefrontal cortex. The data also show the coexistence of NCS‐1 and D 2 at the ultrastructural level. The latter finding suggests a role for NCS‐1 in desensitization of D 2 in the prefrontal cortex. J. Comp. Neurol. 488:464–475, 2005. © 2005 Wiley‐Liss, Inc.