DRD3

G protein-coupled receptor for dopamine, a catecholamine neurotransmitter hormone that functions as the brain's 'reward chemical', driving motivation, reinforcement learning and pleasure. Dopamine binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase. Dopamine receptors can be classified in two categories: (1) DRD3 (together with DRD2 and DRD4) is a D2-type receptor and is coupled to G(i)/G(o) G proteins, mediating inhibition of adenylate cyclase activity, while D1-type receptors (DRD1 and DRD5) are coupled to G(s) G proteins and promote activation of adenylate cyclase activity. D1- and D2-type dopamine receptors have antagonistic effects, particularly in the brain's striatum, where they govern voluntary movement and reward: D1-type receptors generally stimulate neural activity and promotes action, while D2-type receptors tend to inhibit neural activity and suppress movement. DRD3 is primarily expressed in limbic areas of the brain and is involved in the modulation of cognitive, emotional and motor functions: plays a key role in regulating neuronal signaling pathways associated with motivation, reward and behavior. Involved in the incentive salience of drugs: controls responses to drug-related stimuli, making it a key target for reducing addiction to substances like cocaine, morphine, and alcohol. Forms heterotetramers with DRD1 to potentiate beta-arrestin recruitment and mediate locomotor activity (By similarity). Also involved in autophagy regulation: receptor activation stimulates AMPK, which phosphorylates RPTOR and enhances its interaction with MTOR, thereby inhibiting mTORC1 signaling and its downstream target RPS6KB1. This leads to activation of ULK1 and initiation of the autophagy cascade..

Function from UniProtKB (P35462), read 2026-09-23. CC BY 4.0.