ONTOGENIC EXPRESSION OF D2 DOPAMINE RECEPTOR MESSENGER-RNA IN RAT CORPUS STRIATUM

The ontogenetic expression of the D2 dopamine receptor (D2R) mRNA has been characterized in rat corpus striatum by in situ hybridization histochemistry and Northern and slot blot analyses using oligonucleotide probes directed toward either the D2R-A sybtype of the D2R mRNA or to both the D2R-A and D2R-B subtypes of the D2R mRNA. The results showed that both D2R mRNAs were detected in rat striatum at birth, gradually increased until day 16 postnatally (P16), then declined slightly. At early stages of development, the hybridization signal, when viewed under low magnification, was fairly evenly distributed throughout the striatum. However, later in development (P16) a cluster pattern became manifest. Autoradiographic studies using the mu-opiate receptor as an indication of striatal 'patches' in serial, adjacent sections of striatum indicated that the cluster pattern of the D2R mRNA was not associated solely with the patch or matrix compartments of the striatum. A cellular analysis showed that at early developmental stages the quantity of D2R mRNA per cell was very low in striatum. During the first two postnatal weeks, certain subpopulations of striatal neurons evidenced a marked increase in the expression of D2R mRNA per cell. Administration of 6-hydroxydopamine into neonatal rats failed to significantly change the developmental profile of D2R mRNA in the rat striatum of 16- and 32-day-old animals, although the same treatment caused a marked increase in proenkephalin mRNA. These results suggest that the postnatal development of the D2R mRNA in rat striatum correlates well with the ontogeny of the D2 dopamine receptor, that the developmental expression of the D2R mRNA is highly associated with the maturation and differentiation of striatal neurons, and that the development of the D2R mRNA in rat striatum, unlike that of proenkephalin mRNA, can proceed even with reduced dopaminergic afferent input from the substantia nigra.