Gene Number: 1813

Location: 11q23.2

Key Functions: Dopamine signaling, reward system regulation, motor control, cognitive function

DRD2 encodes the dopamine receptor D2, a G protein–coupled receptor (GPCR) that modulates dopaminergic neurotransmission throughout the central nervous system. It functions primarily by inhibiting adenylyl cyclase via Gi/o proteins, thereby reducing intracellular cAMP levels and regulating neuronal excitability, synaptic plasticity, and neurotransmitter release.

Within the striatal regions (caudate nucleus and putamen), DRD2 receptors are densely expressed on medium spiny neurons of the indirect pathway, where they exert inhibitory control over motor output and reinforcement signaling. These striatal DRD2 receptors play a critical role in habit formation, reward learning, and motor regulation, integrating motivational and sensorimotor input for adaptive behavior.

In contrast, extrastriatal DRD2 receptors, located in the prefrontal cortex, hippocampus, thalamus, and limbic structures, modulate executive functions, working memory, emotional regulation, and cognitive control. Their activity contributes to higher-order processes such as attention allocation, decision-making, and affective tone. Dysregulation of these extrastriatal DRD2 populations is strongly implicated in the cognitive and negative symptoms of schizophrenia and in altered top-down control seen in various psychiatric disorders.

Genetic polymorphisms—notably rs1800497 (Taq1A) and rs6277—influence receptor density, binding affinity, and dopaminergic tone. Reduced DRD2 availability, particularly in the striatum, has been linked to addiction susceptibility, anhedonia, and motivational deficits, whereas altered extrastriatal signaling contributes to impaired cognitive flexibility and executive dysfunction. Collectively, DRD2 serves as a key molecular regulator bridging motivation, cognition, and movement through its region-specific functions across the dopaminergic network.