COLOCALIZATION OF THE D-1 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 D-1 dopamine receptor signa l transduction cascade. Both the D-1 receptor and DARPP-32 are found i n the caudate-putamen, but it is not known if they co-localize in the medium-sized spiny neurons. In the present study, double-labelling imm unocytochemistry was used to simultaneously localize the D-1 receptor and DARPP-32 in the rat caudate-putamen. The neuropil was heavily and uniformly immunoreactive for both the D-1 receptor and DARPP-32. All c ell bodies immunopositive for the D-1 receptor were immunopositive for DARPP-32. The D-1 receptor was not detectable, however, in nearly hal f of the DARPP-32-containing cell bodies. DARPP-32 is present in stria topallidal and striatonigral projections. The D-1 receptor co-localize d with DARPP-32 in fibres of the entopeduncular nucleus and the pars r eticulata of the substantia nigra. In the globus pallidus, however, D- 1 receptor immunoreactivity was barely detectable, while DARPP-32 immu nolabelling of axons and axon terminals was intense. These data sugges t that the striatal somata containing both the D-1 receptor and DARPP- 32 project to the entopeduncular nucleus and substantia nigra, whereas somata containing only DARPP-32 immunoreactivity project to the globu s pallidus. Thus, the differences in expression of the D-1 receptor an d of DARPP-32 within striatal cell bodies are likely reflected in thei r projections. The co-localization of the D-1 receptor and DARPP-32 is consistent with the known regulation of DARPP-32 phosphorylation by D -1 receptor activation. The demonstration of a large population of str iatal neurons that contain DARPP-32 but apparently do not contain D-1 receptors substantiates the premise that these cells have an alternati ve signal transduction pathway. Subsequent studies are needed to searc h for a signal transduction pathway for these neurons analogous to the dopamine D-1 receptor pathway. (C) 1997 IBRO. Published by Elsevier S cience Ltd.