The dopamine neurotransmitter belongs to the catecholamines and can therefore be further converted into adrenaline and noreadrenaline. Dopamine has various physiological roles, including learning and memory, motor output and endocrine regulation. It does so by binding and activating dopamine receptors which belong to the G-protein coupled receptor superfamily (GPCR)¹.

The D₄ dopamine receptor (DRD4) belongs to the D₂-like family as do D₂ and D₃ dopamine receptors. Like all GPCRs, it has seven transmembrane spanning membrane regions. Structure-wise, members of the family share high homology in the transmembrane domains and lower homology in the extracellular N-terminal and the intracellular C-terminal domains. Notably, the coding region of the 3^rd intracellular loop of DRD4 is known to undergo extensive polymorphism².

Like many GPCRs, each dopamine receptor subtype can react with more than one G-protein giving rise to different signaling possibilities³. Whereas D₂-like dopamine receptors are generally considered to couple to G_i, and therefore inhibit adenylyl cyclase, the signaling through DRD4 is complicated due to the polymorphisms in the 3^rd intracellular loop. It seems that this region is important to G-coupling as different polyphormisms in the region influence the ability of DRD4 to couple to adenylyl cyclase and G-proteins^4,5. D₄ dopamine receptors also influence Ca²⁺ levels^3,6. They could also interact with G-protein couple inwardly rectifying K⁺ channel to ultimately cause a decrease in the firing rate of neurons⁷.

The distribution of DRD4 mostly includes the brain and is mainly found post-synaptically in dendritic shafts and spines of mammalian striatum⁸.