D<sub>3</sub> receptor | Dopamine receptors | IUPHAR/BPS Guide to PHARMACOLOGY

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D3 receptor

Target not currently curated in GtoImmuPdb

Target id: 216

Nomenclature: D3 receptor

Family: Dopamine receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

Contents:

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 400 3q13.3 DRD3 dopamine receptor D3 52
Mouse 7 446 16 B4 Drd3 dopamine receptor D3 44
Rat 7 446 11q21 Drd3 dopamine receptor D3 132
Previous and Unofficial Names
D3 receptor | dopamine D3 receptor | dopaminergic receptor D3 | D3R
Database Links
Specialist databases
GPCRDB drd3_human (Hs), drd3_mouse (Mm), drd3_rat (Rn)
Other databases
ChEMBL Target CHEMBL234 (Hs), CHEMBL3441 (Mm), CHEMBL3138 (Rn)
DrugBank Target P35462 (Hs)
Ensembl Gene ENSG00000151577 (Hs), ENSMUSG00000022705 (Mm), ENSRNOG00000026772 (Rn)
Entrez Gene 1814 (Hs), 13490 (Mm), 29238 (Rn)
Human Protein Atlas ENSG00000151577 (Hs)
KEGG Gene hsa:1814 (Hs), mmu:13490 (Mm), rno:29238 (Rn)
OMIM 126451 (Hs)
Orphanet ORPHA121179 (Hs)
Pharos P35462 (Hs)
RefSeq Nucleotide NM_000796 (Hs), NM_007877 (Mm), NM_017140 (Rn)
RefSeq Protein NP_000787 (Hs), NP_031903 (Mm), NP_058836 (Rn)
SynPHARM 2633 (in complex with eticlopride)
UniProtKB P35462 (Hs), P30728 (Mm), P19020 (Rn)
Wikipedia DRD3 (Hs)
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the human dopamine D3 receptor in complex with eticlopride
PDB Id:  3PBL
Ligand:  eticlopride
Resolution:  2.89Å
Species:  Human
References:  27
Natural/Endogenous Ligands
dopamine

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]7-OH-DPAT Hs Agonist 9.6 pKd 120
⤷ pKd 9.6 (Kd 2.7x10-10 M) [120]
[3H]7-OH-DPAT Rn Agonist 9.1 pKd 88
⤷ pKd 9.1 (Kd 7.94x10-10 M) [88]
[3H]PD128907 Hs Agonist 9.0 pKd 4
⤷ pKd 9.0 (Kd 9.9x10-10 M) [4]
cariprazine Hs Partial agonist 10.1 pKi 2
⤷ pKi 10.1 (Ki 9x10-11 M) [2]
Description: Binding affinity to human dopamine D3 receptor
lisuride Hs Partial agonist 9.6 pKi 102
⤷ pKi 9.6 [102]
cabergoline Hs Partial agonist 9.1 pKi 102
⤷ pKi 9.1 [102]
terguride Hs Partial agonist 9.0 pKi 102
⤷ pKi 9.0 [102]
BP 897 Hs Partial agonist 9.0 pKi 114
⤷ pKi 9.0 (Ki 1x10-9 M) [114]
roxindole Hs Partial agonist 8.9 pKi 102
⤷ pKi 8.9 [102]
pramipexole Hs Full agonist 8.4 – 8.7 pKi 97,123
⤷ pKi 8.4 – 8.7 [97,123]
(-)-N-porphynorapomorphine Hs Full agonist 8.4 – 8.7 pKi 45,123
⤷ pKi 8.4 – 8.7 [45,123]
rotigotine Hs Agonist 8.4 pKi 43
⤷ pKi 8.4 (Ki 4x10-9 M) [43]
pergolide Hs Partial agonist 8.3 pKi 102,131
⤷ pKi 8.3 (Ki 5.01x10-9 M) [102,131]
7-OH-DPAT Hs Full agonist 7.1 – 8.4 pKi 19,31,45,89,123
⤷ pKi 7.1 – 8.4 (Ki 7.94x10-8 – 3.98x10-9 M) [19,31,45,89,123]
ropinirole Hs Agonist 7.7 pKi 58
⤷ pKi 7.7 (Ki 1.9x10-8 M) [58]
apomorphine Rn Partial agonist 7.7 pKi 132
⤷ pKi 7.7 [132]
7-trans-OH-PIPAT Hs Full agonist 7.7 pKi 31
⤷ pKi 7.7 [31]
bromocriptine Hs Partial agonist 7.1 – 8.2 pKi 45,102,123
⤷ pKi 7.1 – 8.2 [45,102,123]
PD 128907 Hs Full agonist 7.6 – 7.7 pKi 117,123
⤷ pKi 7.6 – 7.7 (Ki 2.51x10-8 – 1.99x10-8 M) [117,123]
quinpirole Rn Full agonist 7.3 – 7.8 pKi 19,132
⤷ pKi 7.3 – 7.8 [19,132]
quinelorane Hs Full agonist 7.2 – 7.4 pKi 103,131
⤷ pKi 7.2 – 7.4 [103,131]
quinpirole Hs Full agonist 6.4 – 8.0 pKi 19,97,103,111,123,131-132,143
⤷ pKi 6.4 – 8.0 (Ki 3.98x10-7 – 1x10-8 M) [19,97,103,111,123,131-132,143]
bromocriptine Rn Full agonist 7.1 pKi 132
⤷ pKi 7.1 [132]
dopamine Hs Full agonist 6.4 – 7.3 pKi 19,45,123,132
⤷ pKi 6.4 – 7.3 [19,45,123,132]
apomorphine Hs Partial agonist 6.1 – 7.6 pKi 19,45,102,123,131
⤷ pKi 6.1 – 7.6 [19,45,102,123,131]
compound 3 [PMID: 23134120] Hs Agonist 6.8 pKi 135
⤷ pKi 6.8 (Ki 1.68x10-7 M) [135]
piribedil Hs Partial agonist 6.6 pKi 102
⤷ pKi 6.6 [102]
HS665 Hs Agonist 6.6 pKi 135
⤷ pKi 6.6 (Ki 2.82x10-7 M) [135]
vilazodone Hs Agonist 7.2 pIC50 59
⤷ pIC50 7.2 (IC50 7.1x10-8 M) [59]
PF-592379 Hs Agonist 6.7 pIC50 33
⤷ pIC50 6.7 (IC50 2.15x10-7 M) [33]
View species-specific agonist tables
Agonist Comments
PF-592379 has no measurable binding to D1, D2 or D5 receptors [33].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]nemonapride Hs Antagonist 10.3 pKd 90
⤷ pKd 10.3 [90]
[3H]spiperone Rn Antagonist 9.9 pKd 61,155
⤷ pKd 9.9 (Kd 1.25x10-10 M) [61,155]
S33084 Hs Antagonist 9.6 pKi 101
⤷ pKi 9.6 (Ki 2.5x10-10 M) [101]
perospirone Hs Antagonist 9.6 pKi 131
⤷ pKi 9.6 (Ki 2.8x10-10 M) [131]
nafadotride Hs Antagonist 9.5 pKi 124
⤷ pKi 9.5 (Ki 3x10-10 M) [124]
nemonapride Hs Antagonist 9.2 – 9.3 pKi 89,140
⤷ pKi 9.2 – 9.3 [89,140]
spiperone Hs Antagonist 9.2 pKi 132
⤷ pKi 9.2 [132]
PG01037 Hs Antagonist 9.2 pKi 56
⤷ pKi 9.2 [56]
flupentixol Hs Antagonist 9.0 pKi 45
⤷ pKi 9.0 (Ki 1.1x10-9 M) [45]
eticlopride Hs Antagonist 8.8 pKi 89,140
⤷ pKi 8.8 [89,140]
NGB 2904 Hs Antagonist 8.8 pKi 147
⤷ pKi 8.8 [147]
sertindole Hs Antagonist 8.0 – 8.8 pKi 7,126,128
⤷ pKi 8.0 – 8.8 (Ki 1x10-8 – 1.6x10-9 M) [7,126,128]
prochlorperazine Hs Antagonist 8.4 pKi 10
⤷ pKi 8.4 (Ki 4.45x10-9 M) [10]
zotepine Hs Antagonist 8.2 pKi 126
⤷ pKi 8.2 (Ki 6.4x10-9 M) [126]
(+)-sulpiride Hs Antagonist 8.1 pKi 91
⤷ pKi 8.1 (Ki 7.99x10-9 M) [91]
haloperidol Hs Antagonist 7.5 – 8.6 pKi 45,129,131,142
⤷ pKi 7.5 – 8.6 [45,129,131,142]
SB 277011-A Hs Antagonist 8.0 pKi 118
⤷ pKi 8.0 (Ki 1x10-8 M) [118]
raclopride Hs Antagonist 7.9 pKi 103
⤷ pKi 7.9 [103]
pimozide Hs Antagonist 7.0 – 8.6 pKi 45,131
⤷ pKi 7.0 – 8.6 [45,131]
loxapine Hs Antagonist 7.7 pKi 128
⤷ pKi 7.7 (Ki 2.1x10-8 M) [128]
mesoridazine Hs Antagonist 7.6 pKi 30
⤷ pKi 7.6 (Ki 2.3x10-8 M) [30]
raclopride Rn Antagonist 7.5 pKi 132
⤷ pKi 7.5 [132]
(+)-butaclamol Rn Antagonist 7.3 – 7.5 pKi 19
⤷ pKi 7.3 – 7.5 [19]
pimozide Rn Antagonist 7.4 pKi 132
⤷ pKi 7.4 [132]
amisulpride Rn Antagonist 7.4 pKi 132
⤷ pKi 7.4 [132]
(+)-S-14297 Hs Antagonist 6.9 – 7.9 pKi 99,103
⤷ pKi 6.9 – 7.9 (Ki 1.26x10-7 – 1.3x10-8 M) [99,103]
(+)-butaclamol Hs Antagonist 6.7 – 8.0 pKi 45,117,140
⤷ pKi 6.7 – 8.0 [45,117,140]
chlorpromazine Hs Antagonist 7.2 – 7.5 pKi 45,131
⤷ pKi 7.2 – 7.5 [45,131]
domperidone Hs Antagonist 7.1 – 7.6 pKi 45,131
⤷ pKi 7.1 – 7.6 [45,131]
sulpiride Hs Antagonist 6.8 – 7.8 pKi 19
⤷ pKi 6.8 – 7.8 (Ki 1.42x10-7 – 1.4x10-8 M) [19]
chlorpromazine Rn Antagonist 7.2 pKi 132
⤷ pKi 7.2 [132]
(+)-UH232 Hs Antagonist 7.0 – 7.4 pKi 45,132
⤷ pKi 7.0 – 7.4 [45,132]
(-)-sulpiride Hs Antagonist 6.7 – 7.7 pKi 45,131,140
⤷ pKi 6.7 – 7.7 (Ki 2.07x10-7 – 2x10-8 M) [45,131,140]
haloperidol Rn Antagonist 7.0 pKi 132
⤷ pKi 7.0 [132]
risperidone Hs Antagonist 7.0 pKi 103
⤷ pKi 7.0 [103]
(+)-UH232 Rn Antagonist 7.0 pKi 132
⤷ pKi 7.0 [132]
domperidone Rn Antagonist 7.0 pKi 132
⤷ pKi 7.0 [132]
promazine Hs Antagonist 6.8 pKi 20
⤷ pKi 6.8 (Ki 1.59x10-7 M) [20]
trans-flupenthixol Hs Antagonist 6.5 pKi 45
⤷ pKi 6.5 (Ki 3x10-7 M) [45]
(+)-sulpiride Rn Antagonist 6.4 pKi 132
⤷ pKi 6.4 [132]
(+)-AJ76 Hs Antagonist 5.9 – 6.2 pKi 103,131
⤷ pKi 5.9 – 6.2 [103,131]
(+)-AJ76 Rn Antagonist 6.0 pKi 132
⤷ pKi 6.0 [132]
clozapine Hs Antagonist 5.2 – 6.3 pKi 45,131
⤷ pKi 5.2 – 6.3 [45,131]
clozapine Rn Antagonist 5.7 pKi 132
⤷ pKi 5.7 [132]
View species-specific antagonist tables
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
SB269652 Hs Negative ~9.0 pKi 46
⤷ pKi ~9.0 (Ki ~1x10-9 M) [46]
Immuno Process Associations
Immuno Process:  Antigen presentation
GO Annotations:  Associated to 2 GO processes
GO:0002031 G protein-coupled receptor internalization IDA
click arrow to show/hide IEA associations
GO:0099149 regulation of postsynaptic neurotransmitter receptor internalization IEA
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
Potassium channel
References:  28,85,115-116,127
Tissue Distribution
Ventral striatum/nucleus accumbens > neostriatum, cerebral cortex, cerebellar cortex.
Species:  Human
Technique:  Autoradiography.
References:  60,75
Brain: nucleus accumbens and islands of Calleja.
Species:  Human
Technique:  in situ hybridization.
References:  77
Brain: mesencephalic dopamine neurons in substantia nigra and ventral tegmental area.
Species:  Rat
Technique:  In situ hybridization.
References:  42
Kidney: proximal tubules
Species:  Rat
Technique:  Immunohistochemistry
References:  107
Brain: Post-synaptic elements of asymmetric synapses of the nucleus accumbens
Species:  Rat
Technique:  Immuno-electron microscopy
References:  86,133
Brain: islands of Cajella, olafactory bulb, pituitary intermediate lobe > nucleus accumbens, molecular layer of the vestibulocerebellum, substantia nigra pars compacta.
Species:  Rat
Technique:  Autoradiography and in situ hybridization.
References:  13,41,49,76,82,88,110,119
Accumbens nucleus, islands of Calleja, bed nucleus of the stria terminalis, hippocampus, mammillary nuclei, substantia nigra.
Species:  Rat
Technique:  in situ hybridization.
References:  15
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays
Measurement of whole-cell potassium current in NG108-15 cells tranfected with the human D3 receptor.
Species:  Human
Tissue:  NG108-15 cells.
Response measured:  Reduction of peak whole-cell potassium current.
References:  85
Measurement of adenylyl cyclase activity in CHO cells transfected with the rat D3 receptor.
Species:  Rat
Tissue:  CHO cells.
Response measured:  Inhibition of adenylyl cyclase.
References:  28
Measurement of extracellular acidification rates in CHO cells transfected with the rat D3 receptor.
Species:  Rat
Tissue:  CHO cells.
Response measured:  Increase in extracellular acidification rates.
References:  28
Measurement of extracellular acidification and D3 receptor membrane density in C6 glioma cells transfected with the rat D3 receptor.
Species:  Rat
Tissue:  C6 glioma cells.
Response measured:  Increase in extracellular acidification rate and receptor density.
References:  35
Measurement of c-fos activation and increased mitogenesis in neuroblastoma-glioma hybrid cells (NG108-15) transfected with the human D3 receptor.
Species:  Human
Tissue:  NG108-15 cells.
Response measured:  Increase in c-fos activation and mitogenesis.
References:  115
Measurement of cAMP accumulation in cultured Xenopus laevis melanophores transfected with the human D3 receptor.
Species:  Human
Tissue:  Cultured Xenopus laevis melanophores.
Response measured:  Inhibition of cAMP accumulation.
References:  116
Measurement of activation of GIRK1 in Xenopus oocytes transfected with the human D3 receptor.
Species:  Human
Tissue:  Xenopus oocytes.
Response measured:  Activation of GIRK1.
References:  146
Measurement of mitogenesis in NG108-15 cells transfected with the human D3 receptor.
Species:  Human
Tissue:  NG108-15 cells.
Response measured:  Increase in mitogenesis.
References:  123
Measurement of melanocyte aggregation in Xenopus melanocytes transfected with the human D3 receptor.
Species:  Human
Tissue:  Xenopus melanocytes.
Response measured:  Stimulation of melanocyte aggregation.
References:  18,117
Measurement of extracellular acidification in CHO cells transfected with the human D3 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Increase in extracellular acidification.
References:  18
Measurement of activation of an 85 pS K+ channel known to be activated by dopamine and the "D2-like" agonist quinpirole.
Species:  Human
Tissue:  Freshly dissociated rat caudate-putamen neurons.
Response measured:  Activation of K+ channel.
References:  84
Measurement of dopamine release from a mesencephalic clonal cell line transfected with the D3 receptor.
Species:  Human
Tissue:  Neuronal mesencephalic MN9D cells.
Response measured:  Inhibition of dopamine release.
References:  141
Measurement of K+-stimulated tyrosine hydroxylase activity in D3 receptor-expressing MN9D cells.
Species:  Human
Tissue:  MN9D cells
Response measured:  Decrease in K+-stimulated tyrosine hydroxylase activity.
References:  108
Measurement of cAMP levels in HEK 293 cells transfected with the human D3 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Inhibition of cAMP accumulation.
References:  93
Measurement of Cl- currents in Xenopus oocytes transfected with murine D3L and D3S receptors.
Species:  Mouse
Tissue:  Xenopus oocytes.
Response measured:  Stimulation of Cl- influx.
References:  130
Measurement of β-arrestin translocation in CHO cells with the human D3 receptor.
Species:  Human
Tissue:  CHO cells
Response measured:  β-arrestin translocation
References:  12,96,149
Physiological Functions
Modulation of motor activity.
Species:  Mouse
Tissue:  In vivo.
References:  136
Inhibition of dopamine release.
Species:  Rat
Tissue:  In vivo.
References:  38,117
Stimulation of yawning and hypothermia.
Species:  Rat
Tissue:  In vivo.
References:  3,38,67,72,98-99,103
Activation increases cell division.
Species:  Rat
Tissue:  CHO cells.
References:  28
Inhibition of locomotor activity.
Species:  Rat
Tissue:  In vivo.
References:  3,37,39,50,65,67,69,83,94,117,124,138-139,144-145
Modulation of sniffing behaviour.
Species:  Rat
Tissue:  In vivo.
References:  37
Modulation of penile erection and ejaculatory behaviour.
Species:  Rat
Tissue:  In vivo.
References:  22,72
Modulation of self-administration of cocaine.
Species:  Rat
Tissue:  In vivo.
References:  21
Modulation of self-stimulation of the ventral tegmental area.
Species:  Rat
Tissue:  In vivo.
References:  39
Modulation of reinforcing effects of cocaine and d-amphetamine.
Species:  Rat
Tissue:  In vivo.
References:  68
Stimulation of the D3 receptor decreases the rate of food-reinforced responding in a fixed-ratio operant paradigm.
Species:  Rat
Tissue:  In vivo.
References:  122
Stimulation of the D3 receptor produces an aversive effect in a conditioned place-preference paradigm.
Species:  Rat
Tissue:  In vivo.
References:  26
Hyperpolarization of neurons and inhibition of cell firing.
Species:  Rat
Tissue:  Substantia nigra pars compacta and ventral tegmental area of rat brain slices.
References:  16
A D3 agonist with relative selectivity for the dopamine D3 receptor, inhibits the firing of both A9 and A10 dopamine neurons and causes current-dependent inhibitions of spontaneously active or glutamate-driven caudate-putamen and nucleus accumbens neurons.
Species:  Rat
Tissue:  Substantia nigra pars compacta and ventral tegmental area dopamine neurons, and caudate-putamen and nucleus accumbens neurons in vivo.
References:  84
Systemic administration of a D3 receptor agonist decreases extracellular dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the nucleus accumbens and dopaminergic neuronal activity in the ventral tegmental area.
Species:  Rat
Tissue:  In vivo.
References:  40
A D3 agonist inhibits substantia nigra pars compacta dopamine single cell firing.
Species:  Rat
Tissue:  In vivo.
References:  71
A D3 agonist inhibits ventral tagmental area dopamine single cell firing.
Species:  Rat
Tissue:  In vivo.
References:  80
Administration of a D3 agonist to freely moving rats decreases dialysate levels of dopamine in the nucleus accumbens.
Species:  Rat
Tissue:  In vivo.
References:  121
Application of a D3 receptor agonist reduces electrically-evoked dopamine release from the nucleus accumbens and striatum.
Species:  Rat
Tissue:  Nucleus accumbens and striatal slices.
References:  152
Modulation of dopamine synthesis.
Species:  Rat
Tissue:  In vivo.
References:  6,47,54,117
Blockade of the D3 receptor inhibits dizocilpine (MK-801)-induced hyperactivity.
Species:  Mouse
Tissue:  In vivo.
References:  81
Blockade of the D3 receptor disrupts drug-associated cue-induced craving and stress-induced craving.
Species:  Rat
Tissue:  In vivo.
References:  5,25,48,51,112,114,148
Blockade of the D3 receptor enhances monoaminergic and cholinergic neurotransmission.
Species:  Rat
Tissue:  In vivo.
References:  73-74,100-101
Application of a D3 receptor agonist reduces electrically-evoked dopamine release from the nucleus accumbens and striatum.
Species:  Rat
Tissue:  Nucleus accumbens and striatal slices.
References:  152
Modulation by the D3 receptor of drug-induced place preference.
Species:  Rat
Tissue:  In vivo.
References:  8,11,24,57,62
Reciprocal regulation of D3 receptor and NMDA receptor through Ca2+/calmodulin-dependent protein kinase II
Species:  Rat
Tissue:  GST-constructs and nucleus accumbens extracts.
References:  86
Selective D3 antagonists induced positive cerebral blood volume (CBV) changes whereas D3 agonism using 7-OH-DPAT induced negative CBV changes.
Species:  Rat
Tissue:  Nucleus accumbens, antero-medial striatum, cingulate cortex, thalamus, interpeduncular region and hypothalamus.
References:  29
Regulation of renal function and blood pressure by D3 receptors.
Species:  Rat
Tissue:  In vivo.
References:  87,153-154
Physiological Consequences of Altering Gene Expression
D3 receptor knockout mice exhibit renin-dependent hypertension.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  9
D3 receptor knockout mice exhibit altered circadian pattern in spinal dopamine synthesis.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  32
D3 receptor knockout mice exhibit reduced anxiety.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  137
D3 receptor knockout mice exhibit neuroadaptive changes which support the role of D3 receptors as autoreceptors.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  79
D3 receptor knockout mice exhibit higher basal levels of extracellular dopamine compared to the wild-type.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  34,64
D3 receptor knockout mice display enhanced hyperactivity when compared to the wild-type, although these effects may be limited.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  1,14,151
D3 receptor knockout mice display a transient increase in activity in a novel environment compared with wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  70,150
D3 receptor knockout mice exhibit increased behavioural sensitivity to combined injections of D1 and D2 class receptor agonists, cocaine and amphetamine.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  151
D3 receptor knockout mice exhibit increased gene expression in striatal neurons following acute administration of cocaine.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  23
D3 receptor knockout mice exhibit aggravation of the development of physical dependence on ethanol.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  106
D3 receptor knockout mice exhibit increased morphine-induced rewarding effects and potentiation of morphine-induced hyperlocomotion.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  105
D3 receptor knockout mice display similar effects (reward/intake) of ethanol as wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  17
D3 receptor knockout mice exhibit increased D1/D2 receptor-mediated intracellular signalling.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  104
D3 receptor knockout mice exhibit increased adiposity induced by a high-fat diet.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  95
D3 receptor knockout mice display increased susceptibility to cocaine addition
Species:  Mouse
Tissue: 
Technique:  Gene knockout
References:  134
Dopamine is more efficacious at the D3 receptor Gly9 compared to Ser9 variant.
Species:  Human
Tissue:  HEK293 cells
Technique:  Binding, adenylate cyclase inhibition, MAPK phosphorylation
References:  63
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
+|Cm|Drd3tm1Stl Cm/+,Drd3tm1Stl/Drd3tm1Stl
involves: 101/H * 129S2/SvPas * C3H/HeH * C3H/HeSn * C57BL/6J		 MGI:88424  MGI:94925  MP:0009748 abnormal behavioral response to addictive substance PMID: 19840852 
Drd3tm1Stl Drd3tm1Stl/Drd3tm1Stl
involves: 129S2/SvPas * C57BL/6		 MGI:94925  MP:0001454 abnormal cued conditioning behavior PMID: 9354330 
Drd2tm1Schm|Drd3tm1Schm Drd2tm1Schm/Drd2tm1Schm,Drd3tm1Schm/Drd3tm1Schm
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:94924  MGI:94925  MP:0001905 abnormal dopamine level PMID: 10391470 
Drd2tm1Schm|Drd3+|Drd3tm1Schm Drd2tm1Schm/Drd2tm1Schm,Drd3tm1Schm/Drd3+
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:94924  MGI:94925  MP:0001905 abnormal dopamine level PMID: 10391470 
Drd3tm1Stl Drd3tm1Stl/Drd3tm1Stl
involves: 129S2/SvPas * C57BL/6		 MGI:94925  MP:0005449 abnormal food intake PMID: 15084447 
Drd2tm1Schm|Drd3tm1Schm Drd2tm1Schm/Drd2tm1Schm,Drd3tm1Schm/Drd3tm1Schm
B6.Cg-Drd2 Drd3		 MGI:94924  MGI:94925  MP:0006001 abnormal intestinal transit time PMID: 16525059 
Drd2tm1Schm|Drd3tm1Schm Drd2tm1Schm/Drd2tm1Schm,Drd3tm1Schm/Drd3tm1Schm
B6.Cg-Drd2 Drd3		 MGI:94924  MGI:94925  MP:0006003 abnormal large intestinal transit time PMID: 16525059 
Drd2tm1Schm|Drd3tm1Schm Drd2tm1Schm/Drd2tm1Schm,Drd3tm1Schm/Drd3tm1Schm
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:94924  MGI:94925  MP:0001392 abnormal locomotor activity PMID: 10391470 
Drd2tm1Schm|Drd3+|Drd3tm1Schm Drd2tm1Schm/Drd2tm1Schm,Drd3tm1Schm/Drd3+
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:94924  MGI:94925  MP:0001392 abnormal locomotor activity PMID: 10391470 
Drd2+|Drd2tm1Schm|Drd3tm1Schm Drd2tm1Schm/Drd2+,Drd3tm1Schm/Drd3tm1Schm
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:94924  MGI:94925  MP:0001392 abnormal locomotor activity PMID: 10391470 
Drd2tm1Schm|Drd3tm1Schm Drd2tm1Schm/Drd2tm1Schm,Drd3tm1Schm/Drd3tm1Schm
B6.Cg-Drd2 Drd3		 MGI:94924  MGI:94925  MP:0001666 abnormal nutrient absorption PMID: 16525059 
Drd3tm1Stl Drd3tm1Stl/Drd3tm1Stl
involves: 129S2/SvPas * C57BL/6		 MGI:94925  MP:0000676 abnormal water content PMID: 15084447 
Drd2tm1Schm|Drd3tm1Schm Drd2tm1Schm/Drd2tm1Schm,Drd3tm1Schm/Drd3tm1Schm
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:94924  MGI:94925  MP:0001262 decreased body weight PMID: 10391470 
Drd2tm1Schm|Drd3tm1Schm Drd2tm1Schm/Drd2tm1Schm,Drd3tm1Schm/Drd3tm1Schm
B6.Cg-Drd2 Drd3		 MGI:94924  MGI:94925  MP:0001262 decreased body weight PMID: 16525059 
Drd3tm1Rmw Drd3tm1Rmw/Drd3tm1Rmw
involves: 129P2/OlaHsd		 MGI:94925  MP:0005643 decreased dopamine level PMID: 12044470 
Drd3tm1Dac Drd3tm1Dac/Drd3tm1Dac
involves: 129S4/SvJae * C57BL/6		 MGI:94925  MP:0001442 decreased grooming behavior PMID: 8700864 
Drd3+|Drd3tm1Dac Drd3tm1Dac/Drd3+
involves: 129S4/SvJae * C57BL/6		 MGI:94925  MP:0001442 decreased grooming behavior PMID: 8700864 
Drd2tm1Schm|Drd3tm1Schm Drd2tm1Schm/Drd2tm1Schm,Drd3tm1Schm/Drd3tm1Schm
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:94924  MGI:94925  MP:0001505 hunched posture PMID: 10391470 
Drd3tm1Stl Drd3tm1Stl/Drd3tm1Stl
involves: 129S2/SvPas * C57BL/6		 MGI:94925  MP:0001399 hyperactivity PMID: 9354330 
Drd3tm1Dac Drd3tm1Dac/Drd3tm1Dac
involves: 129S4/SvJae * C57BL/6		 MGI:94925  MP:0001399 hyperactivity PMID: 8700864 
Drd3+|Drd3tm1Dac Drd3tm1Dac/Drd3+
involves: 129S4/SvJae * C57BL/6		 MGI:94925  MP:0001399 hyperactivity PMID: 8700864 
Drd3tm1Stl Drd3tm1Stl/Drd3tm1Stl
involves: 129S2/SvPas * C57BL/6		 MGI:94925  MP:0005669 increased circulating leptin level PMID: 15084447 
Drd2tm1Schm|Drd3tm1Schm Drd2tm1Schm/Drd2tm1Schm,Drd3tm1Schm/Drd3tm1Schm
B6.Cg-Drd2 Drd3		 MGI:94924  MGI:94925  MP:0003867 increased defecation PMID: 16525059 
Drd2tm1Schm|Drd3tm1Schm Drd2tm1Schm/Drd2tm1Schm,Drd3tm1Schm/Drd3tm1Schm
B6.Cg-Drd2 Drd3		 MGI:94924  MGI:94925  MP:0003911 increased drinking behavior PMID: 16525059 
Drd2tm1Schm|Drd3tm1Schm Drd2tm1Schm/Drd2tm1Schm,Drd3tm1Schm/Drd3tm1Schm
B6.Cg-Drd2 Drd3		 MGI:94924  MGI:94925  MP:0003909 increased eating behavior PMID: 16525059 
Drd3tm1Stl Drd3tm1Stl/Drd3tm1Stl
involves: 129S2/SvPas * C57BL/6		 MGI:94925  MP:0001415 increased exploration in new environment PMID: 9354330 
Drd3tm1Dac Drd3tm1Dac/Drd3tm1Dac
involves: 129S4/SvJae * C57BL/6		 MGI:94925  MP:0001415 increased exploration in new environment PMID: 8700864 
Drd3+|Drd3tm1Dac Drd3tm1Dac/Drd3+
involves: 129S4/SvJae * C57BL/6		 MGI:94925  MP:0001415 increased exploration in new environment PMID: 8700864 
Drd3tm1Stl Drd3tm1Stl/Drd3tm1Stl
involves: 129S2/SvPas * C57BL/6		 MGI:94925  MP:0005458 increased percent body fat PMID: 15084447 
Drd3tm1Rmw Drd3tm1Rmw/Drd3tm1Rmw
involves: 129P2/OlaHsd		 MGI:94925  MP:0001409 increased stereotypic behavior PMID: 12044470 
Drd3tm1Stl Drd3tm1Stl/Drd3tm1Stl
involves: 129S2/SvPas * C57BL/6		 MGI:94925  MP:0005455 increased susceptibility to weight gain PMID: 15084447 
Drd3tm1Stl Drd3tm1Stl/Drd3tm1Stl
involves: 129S2/SvPas * C57BL/6		 MGI:94925  MP:0010024 increased total body fat amount PMID: 15084447 
Drd3tm1Dac Drd3tm1Dac/Drd3tm1Dac
involves: 129S4/SvJae * C57BL/6		 MGI:94925  MP:0002574 increased vertical activity PMID: 8700864 
Drd3+|Drd3tm1Dac Drd3tm1Dac/Drd3+
involves: 129S4/SvJae * C57BL/6		 MGI:94925  MP:0002574 increased vertical activity PMID: 8700864 
Drd2tm1Schm|Drd3tm1Schm Drd2tm1Schm/Drd2tm1Schm,Drd3tm1Schm/Drd3tm1Schm
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:94924  MGI:94925  MP:0002082 postnatal lethality PMID: 10391470 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Major affective disorder 1; MAFD1
Synonyms: Bipolar affective disorder
Manic depressive-psychosis
OMIM: 125480
Role:  The Ba1I polymorphism has been associated with bipolar disorder
References:  109
Disease:  Schizophrenia
Disease Ontology: DOID:5419
OMIM: 181500
Orphanet: ORPHA3140
Role:  The Ba1I restriction fragment length polymorphism (corresponding to a point mutation in the 1st exon and resulting in a serine-to-glycine substitution in the N-terminal extracellular domain of the receptor) has been associated with schizophrenia.
References:  36,66,92
Disease:  Tremor, hereditary essential, 1; ETM1
Synonyms: Essential tremor [Disease Ontology: DOID:4990]
Hereditary essential tremor [Orphanet: ORPHA862]
Disease Ontology: DOID:4990
OMIM: 190300
Orphanet: ORPHA862
Comments:  Gly9 variant confers disease risk
References:  63
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Type Species Amino acid change Nucleotide change Description Reference
Missense Human S9G Gain of function mutation. Functional variant of the dopamine D3 receptor which is associated with risk and age-at-onset of essential tremor 63
General Comments
Alternative splicing leads to a 425aa isoform in mouse [44] and several shorter presumably inactive isoforms in rat [53] and human [125]. Two polymorphic variants [Ser9] and [Gly9] in human [78]. The organization of the coding sequence of the human gene has been established [55]. Anti-psychotic drugs display closely similar or slightly lower antagonist affinity at D3 compared to D2 receptors. S(+)14297, initially reported as a D3 receptor antagonist [103] displays full agonist activity in two functional assays [113].

References

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