Localization of dopamine D 3 receptor mRNA in the rat brain using in situ hybridization histochemistry: comparison with dopamine D 2 receptor mRNA

Abstract

The messenger RNA (mRNA) of the recently characterized D 3 dopamine receptor was visualized on rat brain sections using in situ hybridization with a 32P-labeled ribonucleic acid probe corresponding to a major part of the third cytoplasmic loop, a domain in which D 2 and D 3 dopamine receptors display little homology. For the purpose of comparison, D 2 receptor mRNA was also specifically visualized on adjacent sections. The areas that expressed D 2 and/or D 3 receptors were also compared with those previously detected using [ 125I]iodosulpride, a ligand that binds to both D 2 and D 3 receptors with a similar affinity. The localization of D 3 receptor mRNa markedly differs from that of D 2 receptor mRNA. Whereas D 2 receptor mRNA is expressed in all major brain areas receiving dopaminergic projections, particularly in the whole striatal complex, D 3 receptor mRNA is expressed in a more restricted manner. It is mainly detected in telencephalic areas receiving dopaminergic inputs from the A 10 cell group, e.g. accumbens nucleus, islands of Calleja, bed nucleus of the stria terminalis and other limbic areas such as the hippocampus and the mammillary nuclei. D 2 and D 3 receptor mRNAs were also detected at the level of the substantia nigra, suggesting that these receptors function as both autoreceptor and postsynaptic receptors. In several dopaminergic projection areas, e.g. ventral striatum, septal or mammillary nuclei, the distribution of D 2 and D 3 receptor mRNAs appeared complementary without overlap. The distribution of [ 125I]iodosulpride binding sites generally overlapped that of D 2 or D 3 receptor mRNAs, the latter being most abundant in dopaminergic areas known to be associated with cognitive and emotional functions.