DRD1

DRD1, or dopamine receptor D1, is a G protein-coupled receptor encoded by the DRD1 gene in humans. It is a member of the D1-like family of dopamine receptors, along with DRD5, and functions as a postsynaptic receptor for dopamine in the central nervous system. The receptor is a seven-transmembrane domain protein that belongs to the larger class of GPCRs.

D1 receptors primarily couple to Gs/olf proteins, activating adenylyl cyclase and increasing intracellular cyclic AMP (cAMP). This signaling cascade leads to activation of protein kinase A (PKA) and downstream targets such as DARPP-32, influencing neuronal excitability and synaptic plasticity. DRD1 is widely expressed in brain regions including the striatum (caudate nucleus and putamen), nucleus accumbens, and prefrontal cortex, with additional expression in other cortical and limbic areas. In the basal ganglia, D1 receptors are concentrated on the direct pathway neurons and contribute to the modulation of motor control, motivation, reward, learning, and cognition.

Pharmacology and research use: endogenous dopamine is the natural ligand. Pharmacological tools include selective D1-like agonists and antagonists used to study signaling and behavior; examples include agonists such as SKF-38393 or SKF-81297 and antagonists such as SCH-23390. These agents aid in dissecting the role of D1 signaling in various neural processes, though clinical use is limited by side effects and complex dopaminergic regulation.

Clinical significance: altered D1 receptor signaling has been investigated in disorders such as Parkinson’s disease, schizophrenia, and substance use disorders. DRD1 and its signaling pathways are subjects of ongoing research for potential therapeutic strategies targeting cognitive function, mood, and motor symptoms. Genetic variations in DRD1 have been studied for associations with behavioral traits and susceptibility to neuropsychiatric conditions, though findings are not yet conclusive.