HETEROGENEOUS DISTRIBUTION OF D(1)-RECEPTOR, D(2)-RECEPTOR AND D(5)-RECEPTOR MESSENGER-RNAS IN MONKEY STRIATUM

The primate striatum has a compartmental organization reflected both i n the topography of its afferent projections and in the segregation of its morphologically similar but neurochemically distinct efferent neu rons. Discretely projecting mesostriatal neurons release dopamine (DA) which modulates the responses of striatal neurons to other afferent i nputs, Multiple DA receptor (DAR) subtypes have been cloned and charac terized and mapping their cellular expression is crucial for understan ding the influence of DA on striatal function. We report the distribut ion of mRNAs for D1, D2 and D5 DAR subtypes (DtR, D2R and D5R) in the striatum of cynomolgus monkeys (Macaca fascicularis) studied by in sit u hybridization histochemistry (ISH) using monkey-specific cRNA probes . Adjacent sections were stained for calbindin immunoreactivity to dis tinguish striosomal and matrix compartments for comparison with the pa tterns obtained with ISH. In the caudate nucleus, DR mRNA was concentr ated in calbindin-poor striosomes where dense grain clusters were seen overlying the majority of medium-sized neurons (diameter approximatel y 15 mum). D1R mRNA localization was relatively homogeneous in the put amen. By contrast, the distributions of D2R and D5R mRNAs showed no cl ear preference for the striosomal or matrix compartments of either cau date nucleus or putamen. In the ventral striatum (nucleus accumbens. o lfactory tubercle and ventral portions of caudate nucleus and putamen) , expression of D1R and D2R mRNA was sparse relative to dorsal striatu m, while D5R mRNA expression was roughly equal in ventral and dorsal s triatum. Circumscribed zones of hybridization associated with islands of tightly packed small cells occurred with all three DAR mRNA subtype s in the ventral striatum. Large, putative cholinergic neurons which w ere seen in both the striatum and the adjacent basal forebrain, hybrid ized strongly with D2R and D5R cRNA probes but not with the D1R probe. The different yet partially overlapping regional and cellular express ions of DIR, D2R and D5R mRNAs suggest that the corresponding receptor subtypes subserve distinct functions in striatal neuronal processing.