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D3 dopamine receptor is a protein that in humans is encoded by the DRD3 gene.

This gene encodes the D3 subtype of the dopamine receptor. The D3 subtype inhibits adenylyl cyclase through inhibitory G-proteins. This receptor is expressed in phylogenetically older regions of the brain, suggesting that this receptor plays a role in cognitive and emotional functions. The dopamine-D3 receptor is highly concentrated in the nucleus accumbens and is also influential in the medial prefrontal cortex. Action at this receptor is correlated with reinforcement and reward systems through its influence on Protein kinase A (PKA) regulation of the GABA receptor GABAA. It is a target for drugs which treat schizophrenia, drug addiction, and Parkinson's disease. Alternative splicing of this gene results in multiple transcript variants that would encode different isoforms, although some variants may be subject to nonsense-mediated decay (NMD).

D3 agonists like 7-OH-DPAT, pramipexole, and rotigotine, among others, display antidepressant effects in rodent models of depression.

Agonists

 * trans-N-{4-[4-(2,3-Dichlorophenyl)-1-piperazinyl]cyclohexyl}-3-methoxybenzamide, full agonist, > 200-fold binding selectivity over D4, D2, 5-HT1A, and α1-receptors
 * (-)-7-{[2-(4-Phenylpiperazin-1-yl)ethyl]propylamino}-5,6,7,8-tetrahydronaphthalen-2-ol
 * 5-OH-DPAT
 * 7-OH-DPAT
 * 8-OH-PBZI (cis-8-Hydroxy-3-(n-propyl)-1,2,3a,4,5,9b-hexahydro-1H-benz[e]indole)
 * Apomorphine (non-selective dopamine agonist)
 * Bromocriptine (non-selective dopamine agonist)
 * CJ-1639
 * compound R,R-16: 250x binding selectivity over D2
 * Dopamine (endogenous agonist)
 * ES609
 * FAUC 54
 * FAUC 73
 * PD-128,907
 * PF-219,061 (extremely selective)
 * PF-592,379
 * Piribedil (non-selective dopamine agonist)
 * Pramipexole (non-selective dopamine agonist)
 * Quinelorane (also D2 agonist)
 * Quinpirole (also D2 agonist)
 * Ropinirole (non-selective dopamine agonist)
 * Rotigotine (non-selective dopamine agonist)

Partial agonists

 * Aripiprazole (non-selective)
 * BP-897
 * Buspirone (non-selective)
 * CJB 090
 * CJ-1037 (extremely selective)
 * FAUC 460 (highly selective)
 * FAUC 346 (highly selective)
 * Pardoprunox (non-selective)
 * Roxindole (possibly a partial agonist at the D3 autoreceptors, non-selective)
 * OS-3-106
 * UH-232
 * WW-III-55

Antagonists

 * Amisulpride (non-selective)
 * Blonanserin
 * Cyproheptadine (non-selective)
 * PG 01037
 * Domperidone (peripheral D2 and D3 antagonist)
 * FAUC 365, silent antagonist, subtype selective
 * GR-103,691
 * GSK598809 (highly selective)
 * Haloperidol (non-selective)
 * N-(4-(4-(2,3-Dichloro- or 2-methoxyphenyl)piperazin-1-yl)butyl)heterobiarylcarboxamides
 * Nafadotride
 * NGB-2904
 * PNU-99,194 (moderately selective over D2)
 * Raclopride (also D2 antagonist)
 * S-14,297 (selective)
 * S33084
 * SB-277011-A, selective D3 antagonist, 80x selectivity over D2 with no partial agonist effects, used in drug addiction research as a potential therapy for addiction to several different drugs
 * SR 21502 (highly selective)
 * Sulpiride (also D2 antagonist)
 * U99194
 * YQA14 (high affinity and selectivity)
 * Risperidone

Interactions
Dopamine receptor D3 has been shown to interact with CLIC6 and EPB41L1.