DRD3

DRD3

Target · GPCR

DRD3 Dopamine receptor D3 · D2-type dopamine receptor

DRD3 (dopamine receptor D3) is a G protein-coupled receptor for dopamine, the catecholamine neurotransmitter often described as the brain's 'reward chemical'. It is a D2-type receptor that couples to G(i)/G(o) proteins and is expressed mainly in limbic areas of the brain. Browse Assay Genie's current range of DRD3 research reagents below, or read on for the biology behind the target.

Cell membrane receptorG(i)/G(o)-coupled GPCRLimbic brain expression
400 aa
Protein length
~44 kDa
Molecular weight
3q13.31
Gene locus
GPCR
Receptor class
Target information

What is DRD3 (dopamine receptor D3)?

DRD3 binds dopamine, which causes a conformation change that triggers signalling through guanine nucleotide-binding proteins (G proteins) and modulates downstream effectors such as adenylate cyclase. As a D2-type receptor, together with DRD2 and DRD4, DRD3 couples to G(i)/G(o) proteins and mediates inhibition of adenylate cyclase activity. The D1-type receptors, DRD1 and DRD5, instead couple to G(s) proteins and activate adenylate cyclase. The two types have antagonistic effects, particularly in the striatum, where they govern voluntary movement and reward: D1-type receptors generally stimulate neural activity and promote action, while D2-type receptors tend to inhibit neural activity and suppress movement.

DRD3 is primarily expressed in limbic areas of the brain and modulates cognitive, emotional and motor functions. It helps regulate neuronal signalling pathways linked to motivation, reward and behaviour, and it is involved in the incentive salience of drugs, controlling responses to drug-related stimuli. This makes it a key target in work on reducing addiction to substances such as cocaine, morphine and alcohol. DRD3 forms heterotetramers with DRD1, which potentiate beta-arrestin recruitment and mediate locomotor activity. It also contributes to autophagy regulation: receptor activation stimulates AMPK, which phosphorylates RPTOR and enhances its interaction with MTOR. This inhibits mTORC1 signalling and its downstream target RPS6KB1, leading to activation of ULK1 and initiation of the autophagy cascade.

The DRD3 gene encodes the D3 subtype of the five (D1-D5) dopamine receptors and belongs to the G protein-coupled receptor 1 family. Genetic variation in the gene may be associated with susceptibility to hereditary essential tremor 1. Alternative splicing produces transcript variants encoding different isoforms, although some variants may be subject to nonsense-mediated decay. Mouse and rat both carry a Drd3 ortholog.

Addiction neurobiology

DRD3 controls responses to drug-related stimuli and the incentive salience of drugs, making it a key target in studies of cocaine, morphine and alcohol addiction.

Reward and motivation circuits

DRD3 regulates neuronal signalling linked to motivation, reward and behaviour, and is expressed mainly in limbic brain regions.

GPCR signalling and heteromers

DRD3 couples to G(i)/G(o) to inhibit adenylate cyclase and forms heterotetramers with DRD1 that potentiate beta-arrestin recruitment.

Autophagy and mTORC1 signalling

DRD3 activation stimulates AMPK and inhibits mTORC1 signalling, leading to ULK1 activation and initiation of autophagy.

Background

DRD3 frequently asked questions

What does DRD3 do?

DRD3 is a G protein-coupled receptor for dopamine. On dopamine binding it signals through G(i)/G(o) proteins to inhibit adenylate cyclase. It modulates cognitive, emotional and motor functions, regulates motivation and reward signalling, and can also stimulate autophagy through AMPK and mTORC1 inhibition.

How does DRD3 differ from other dopamine receptors?

DRD3 is one of five dopamine receptors (D1-D5). With DRD2 and DRD4 it forms the D2-type group, which couples to G(i)/G(o) and inhibits adenylate cyclase. DRD1 and DRD5 are D1-type and couple to G(s). DRD3 is primarily expressed in limbic areas of the brain.

Is DRD3 linked to disease or conserved in rodents?

NCBI Gene notes that genetic variation in DRD3 may be associated with susceptibility to hereditary essential tremor 1. The gene has mouse and rat orthologs, both named Drd3; check the datasheet of any product for its validated reactivity.

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Related targets

Other dopamine receptors, including the D1-type and D2-type members that act alongside DRD3 in striatal and limbic signalling.

Gene and protein annotations from HGNC, NCBI Gene and UniProt P35462; product specifications from Assay Genie datasheets.

DRD3 Product listing