Co-localization of dopamine D1 (D1R) and D3 receptors (D3R) in specific neuronal populations in the striatum and nucleus accumbens suggests that their cross-talk in the regulation of rewarding mechanisms and emotional and cognitive processes and in the development of motor dysfunctions might involve direct interactions. This paper summarizes recent data showing that D1R and D3R form a receptor heteromer in the striatum. A unique characteristic of this receptor complex is a synergistic interaction by which D3R stimulation increases D1R agonist affinity, allows a stronger stimulatory coupling of the D1R to the cAMP system and potentiates D1R-mediated behaviour. The putative role of the D1R-D3R heteromer in the development of motor dysfunctions is also discussed.
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