Dopamine receptor D₃ (DRD3) is a protein belonging to the dopamine receptor family of [[ G protein-coupled receptor]]s. In humans, it is encoded by the DRD3 gene located on chromosome 3q13.3.

The D₃ receptor belongs to the D2-like receptor subfamily, which also includes D2 and D4 receptors. It couples primarily to Gi/Go proteins, leading to inhibition of adenylyl cyclase and reduced intracellular cAMP levels.

The D₃ receptor displays the highest binding affinity for dopamine among dopamine receptor subtypes, making it a key regulator of tonic dopamine signaling.

D₃ receptors are primarily expressed in limbic brain regions such as the nucleus accumbens, islands of Calleja, and olfactory tubercle. Their distribution in phylogenetically older brain areas suggests an important role in emotion, motivation, and cognition.

Activation of the D₃ receptor regulates dopamine release and modulates neuronal excitability. Preclinical and clinical studies implicate it in:

The DRD3 Ser9Gly polymorphism (rs6280) alters receptor binding characteristics and has been studied in relation to:

D₃ ligands include:

Many of these ligands are used clinically in Parkinson's disease or schizophrenia, while others remain experimental.