The D₅ dopamine receptor (D₅ 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 hormone secretion. 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 D₅ receptor is widely distributed throughout the brain with the highest expression in the cerebral cortex, hippocampus and striatum. In the periphery, the D₅ receptor has been localized in the adrenal cortex, kidney and intestinal tract.

The exact physiological function of the D₅ receptor subtype remains poorly understood. Studies with D₅ receptor knockout mice have shown no overt alterations in locomotor or cognitive functions. However, knockout mice do develop severe hypertension suggesting a role of the D₅ receptor in the modulation of neuronal pathways regulating blood pressure responses.^2,3