The D₃ Dopamine Receptor (D₃ receptor) is one of five receptors that mediate the effects of the catecholamine neurotransmitter dopamine. Dopamine regulates a variety of functions including locomotor activity, emotion, positive reinforcement, food intake, and endocrine regulation. The dopaminergic system has been extensively studied in the last thirty years mainly because its dysregulation has been linked to several neurological and neuropsychiatric diseases including Parkinson’s disease and schizophrenia.¹

All five dopamine receptors belong to the 7-transmembrane domain, G protein-coupled receptor (GPCR) superfamily.

Historically, the five receptors have been divided into two subfamilies based on pharmacological and structural considerations: the D₁-like subfamily (that includes the D₁ and D₅ subtypes) and the D₂-like subfamily (that includes the D₂-, D₃- and D₄ subtypes).¹

The D₁-like receptors are coupled to G_s-type G proteins and enhance adenylate cyclase activity while the D₂-like receptors are coupled to G_i-type G proteins and inhibit adenylate cyclase activity.¹

The D₃ receptor distribution in the brain is relatively restricted to limbic areas such as striatum, islands of Calleja and olfactory tubercle.  In the periphery, it is expressed in the kidney particularly in proximal tubules.¹

The exact physiological function of the D₃ receptor remains to be fully elucidated. In studies using D₃ receptor knockout mice, the most prominent dysfunction was the development of rennin-dependent hypertension. Potential roles in reinforcement and reward behaviors have also been suggested as well as roles in neuropsychiatric disorders such as drug abuse and schizophrenia.²