Co-localization of the D1 dopamine receptor in a subset of DARPP-32-containing neurons in rat caudate-putamen.

DARPP-32 (dopamine- and cyclic AMP-regulated phosphoprotein, apparent molecular weight of 32,000) is part of the D1 dopamine receptor signal transduction cascade. Both the D1 receptor and DARPP-32 are found in the caudate putamen, but it is not known if they co-localize in the medium-sized spiny neurons. In the present study, double-labelling immunocytochemistry was used to simultaneously localize the D1 receptor and DARPP-32 in the rat caudate-putamen. The neuropil was heavily and uniformly immunoreactive for both the D1 receptor and DARPP-32. All cell bodies immunopositive for the D1 receptor were immunopositive for DARPP-32. The D1 receptor was not detectable, however, in nearly half of the DARPP-32-containing cell bodies. DARPP-32 is present in striatopallidal and striatonigral projections. The D1 receptor co-localized with DARPP-32 in fibres of the entopeduncular nucleus and the pars reticulata of the substantia nigra. In the globus pallidus, however, D1 receptor immunoreactivity was barely detectable, while DARPP-32 immunolabelling of axons and axon terminals was intense. These data suggest that the striatal somata containing both the D1 receptor and DARPP-32 project to the entopeduncular nucleus and substantia nigra, whereas somata containing only DARPP-32 immunoreactivity project to the globus pallidus. Thus, the differences in expression of the D1 receptor and of DARPP-32 within striatal cell bodies are likely reflected in their projections. The co-localization of the D1 receptor and DARPP-32 is consistent with the known regulation of DARPP-32 phosphorylation by D1 receptor activation. The demonstration of a large population of striatal neurons that contain DARPP-32 but apparently do not contain D1 receptors substantiates the premise that these cells have an alternative signal transduction pathway. Subsequent studies are needed to search for a signal transduction pathway for these neurons analogous to the dopamine D1 receptor pathway.