Location, Location, Location: The Expression of D3 Dopamine Receptors in the Nervous System

When the rat D3 dopamine receptor (D3R) was cloned and the distribution of its mRNA examined in 1990-1991, it attracted attention due to its peculiar distribution in the brain quite different from that of its closest relative, the D2 receptor. In the rat brain, the D3R mRNA is enriched in the limbic striatum as opposed to the D2 receptor, which is highly expressed in the motor striatal areas. Later studies in the primate and human brain confirmed relative enrichment of the D3R in the limbic striatum but also demonstrated higher abundance of the D3R in the primate as compared to the rodent brain. Additionally, in the rodent brain, the D3R in the dorsal striatum appears to be co-expressed with the D1 dopamine receptor-bearing striatal neurons giving rise to the direct output striatal pathway, although the picture is less clear with respect to the nucleus accumbens. In contrast, in the primate striatum, the D3R co-localizes with the D2 receptor throughout the basal ganglia as well as in extrastriatal brain areas. The relative abundance of the D3R in the limbic striatum, its output structures, secondary targets, and some of the other connected limbic territories may underpin its role in reward, drug dependence, and impulse control. Selective expression of D3R in the brain proliferative areas may point to its important role in the neural development as well as in neurodevelopmental abnormalities associated with schizophrenia and other developmental brain disorders.