D2 receptor

Target id: 215

Nomenclature: D2 receptor

Family: Dopamine receptors

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Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 443 11q23 DRD2 dopamine receptor D2 8,43
Mouse 7 444 9 A5.3 Drd2 dopamine receptor D2 83
Rat 7 444 8q24 Drd2 dopamine receptor D2 8,23
Gene and Protein Information Comments
The human D2 receptor exists as two alternatively spliced isoforms [42]. The 443 amino acid receptor is the long form (D2L). The short form (D2S) is 414 amino acids long.
Previous and Unofficial Names
D2A and D2B | dopamine D2 receptor | dopamine receptor 2 | D2 receptor | D2R | D2(415) and D2(444)
Database Links
Specialist databases
GPCRDB drd2_human (Hs), drd2_mouse (Mm), drd2_rat (Rn)
Other databases
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
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 Affinity Units Reference
rotigotine Hs Agonist 10.2 pKi 36
pKi 10.2 (Ki 6x10-11 M) [36]
aripiprazole Rn Partial agonist 9.7 pKi 99
pKi 9.7 [99]
brexpiprazole Hs Partial agonist 9.5 pKi 71
pKi 9.5 (Ki 3x10-10 M) [71]
lisuride Hs Partial agonist 9.2 – 9.5 pKi 81
pKi 9.2 – 9.5 [81]
aripiprazole Hs Partial agonist 9.1 pKi 130
pKi 9.1 (Ki 8x10-10 M) [130]
cabergoline Hs Partial agonist 9.0 – 9.2 pKi 81
pKi 9.0 – 9.2 [81]
terguride Hs Partial agonist 9.1 pKi 81
pKi 9.1 [81]
roxindole Hs Partial agonist 8.6 pKi 81
pKi 8.6 [81]
UNC9975 Hs Biased agonist 8.6 pKi 3
pKi 8.6 (Ki 2.6x10-9 M) [3]
Description: β-arrestin 2 biased agonist.
UNC0006 Hs Biased agonist 8.3 pKi 3
pKi 8.3 (Ki 5x10-9 M) [3]
Description: β-arrestin 2 biased agonist.
cariprazine Hs Partial agonist 8.2 pKi 1
pKi 8.2 (Ki 5.7x10-9 M) [1]
Description: Binding affinity to human dopamine D2L receptor
MLS1547 Hs Biased agonist 8.2 pKi 39
pKi 8.2 (Ki 5.9x10-9 M) [39]
Description: Biased agonist for G-protein coupling to Gi.
(-)-N-porphynorapomorphine Hs Full agonist 7.5 – 8.9 pKi 40,97
pKi 7.5 – 8.9 [40,97]
ropinirole Hs Agonist 8.1 pKi 47
pKi 8.1 (Ki 7.2x10-9 M) [47]
LP-44 Hs Agonist 8.1 pKi 66
pKi 8.1 (Ki 7.3x10-9 M) [66]
sumanirole Hs Full agonist 8.1 pKi 78
pKi 8.1 (Ki 9x10-9 M) [78]
bromocriptine Hs Full agonist 7.3 – 8.3 pKi 40,81,97
pKi 7.3 – 8.3 [40,81,97]
apomorphine Rn Partial agonist 7.6 pKi 114
pKi 7.6 [114]
pergolide Hs Full agonist 7.5 – 7.6 pKi 81
pKi 7.5 – 7.6 [81]
bromocriptine Rn Partial agonist 7.3 pKi 114
pKi 7.3 [114]
UNC9994 Hs Biased agonist 7.1 pKi 3
pKi 7.1 (Ki 7.9x10-8 M) [3]
Description: β-arrestin 2 biased agonist.
compound 3 [PMID: 23134120] Hs Agonist 6.9 pKi 115
pKi 6.9 (Ki 1.18x10-7 M) [115]
piribedil Hs Partial agonist 6.8 – 6.9 pKi 81
pKi 6.8 – 6.9 [81]
LP-211 Hs Agonist 6.8 pKi 67
pKi 6.8 (Ki 1.42x10-7 M) [67]
LP-12 Hs Agonist 6.7 pKi 66
pKi 6.7 (Ki 2.24x10-7 M) [66]
apomorphine Hs Partial agonist 5.7 – 7.5 pKi 24,40,81,97,112
pKi 5.7 – 7.5 [24,40,81,97,112]
7-OH-DPAT Hs Full agonist 5.6 – 7.6 pKi 24,40,70
pKi 5.6 – 7.6 [24,40,70]
HS665 Hs Agonist 6.3 pKi 115
pKi 6.3 (Ki 4.5x10-7 M) [115]
quinpirole Hs Full agonist 4.9 – 7.7 pKi 24,80,87,112,114,123
pKi 4.9 – 7.7 [24,80,87,112,114,123]
pramipexole Hs Full agonist 5.1 – 7.4 pKi 80,97
pKi 5.1 – 7.4 [80,97]
7-OH-DPAT Rn Full agonist 6.2 pKi 32
pKi 6.2 [32]
dopamine Hs Full agonist 4.7 – 7.2 pKi 24,40,97
pKi 4.7 – 7.2 [24,40,97]
PD 128907 Hs Full agonist 5.4 – 6.4 pKi 89,97
pKi 5.4 – 6.4 [89,97]
dopamine Rn Full agonist 5.3 – 6.4 pKi 99,114
pKi 5.3 – 6.4 [99,114]
7-trans-OH-PIPAT Hs Full agonist 5.6 pKi 32
pKi 5.6 [32]
quinelorane Hs Full agonist 5.5 – 5.7 pKi 82,112
pKi 5.5 – 5.7 [82,112]
benzquinamide Hs Agonist 5.4 pKi 44
pKi 5.4 (Ki 3.964x10-6 M) [44]
quinpirole Rn Full agonist 5.2 pKi 114
pKi 5.2 [114]
UNC9975 Hs Biased agonist 9.0 pEC50 3
pEC50 9.0 (EC50 1.1x10-9 M) [3]
Description: This compound shows biased agonism towards D2-mediated β-arrestin-2 translocation measured using the Tango assay.
UNC0006 Hs Biased agonist 8.9 pEC50 3
pEC50 8.9 (EC50 1.2x10-9 M) [3]
Description: Biased agonist of D2-mediated β-arrestin-2 translocation measured using the Tango assay.
UNC9994 Hs Biased agonist 8.2 pEC50 3
pEC50 8.2 (EC50 6.1x10-9 M) [3]
Description: This compound shows biased agonism towards D2-mediated β-arrestin-2 translocation measured using the Tango assay.
aripiprazole Hs Partial agonist 7.4 pEC50 3
pEC50 7.4 (EC50 3.8x10-8 M) [3]
Description: Measuring cAMP production via the Gi-coupled signaling pathway
vilazodone Hs Agonist 6.2 pIC50 49
pIC50 6.2 (IC50 6.66x10-7 M) [49]
View species-specific agonist tables
Agonist Comments
Terguride and roxindole have been reported to be partial agonists at the D2S receptor and antagonists at the D2L receptor.
Although benzquinamide has higher affinity for α-adrenoceptors, it is suggested in [44] that it is more likely that drug-induced modulation of D2 receptor activity is responsible for the drug's antiemetic action.
​Allosteric modulation of the D2 receptor by SB269652 only occurs when D2 receptor dimers form, with the ligand assuming a 'bitopic' pose and interacting with different sites on each of the two protomers in the dimer [65].
UNC0006, UNC9994 and UNC9975 are partial biased agonists of β-arrestin 2 recruitment at the D2 receptor as measured using three different assays (β-arrestin-2 translocation Tango assay, DiscoveRx assay and BRET-based β-arrestin-2 recruitment assay) [3]. Tango assay pEC50 values and binding Kis are provided in the table above.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]nemonapride Hs Antagonist 10.9 pKd 72
pKd 10.9 [72]
[3H]spiperone Rn Antagonist 10.2 pKd 23,50,133
pKd 10.2 (Kd 5.7x10-11 M) [23,50,133]
[3H]raclopride Rn Antagonist 8.9 pKd 62
pKd 8.9 (Kd 1.2x10-9 M) [62]
[3H]N-methylspiperone Rn Antagonist 10.7 pKi 99
pKi 10.7 [99]
benperidol Hs Antagonist 10.6 pKi 106
pKi 10.6 (Ki 2.7x10-11 M) [106]
blonanserin Hs Antagonist 9.9 pKi 85
pKi 9.9 (Ki 1.4x10-10 M) [85]
pipotiazine Hs Antagonist 9.7 pKi 113
pKi 9.7 (Ki 2x10-10 M) [113]
risperidone Hs Antagonist 9.4 pKi 10
pKi 9.4 (Ki 4.4x10-10 M) [10]
perphenazine Hs Antagonist 8.9 – 9.6 pKi 59,103
pKi 8.9 – 9.6 (Ki 1.4x10-9 – 2.6x10-10 M) [59,103]
perospirone Hs Antagonist 9.2 pKi 104
pKi 9.2 (Ki 6x10-10 M) [104]
eticlopride Hs Antagonist 9.2 pKi 70,119
pKi 9.2 [70,119]
trifluoperazine Hs Antagonist 8.9 – 9.0 pKi 59,105
pKi 8.9 – 9.0 (Ki 1.3x10-9 – 9.6x10-10 M) [59,105]
asenapine Hs Antagonist 8.9 pKi 109
pKi 8.9 (Ki 1.2x10-9 M) [109]
terguride Hs Antagonist 8.9 pKi 81
pKi 8.9 [81]
spiperone Rn Antagonist 8.4 – 9.4 pKi 70,82,114,119
pKi 8.4 – 9.4 [70,82,114,119]
fluphenazine Hs Antagonist 8.8 pKi 96
pKi 8.8 (Ki 1.44x10-9 M) [96]
flupentixol Hs Antagonist 8.8 pKi 40
pKi 8.8 (Ki 1.5x10-9 M) [40]
nafadotride Rn Antagonist 8.8 pKi 99
pKi 8.8 [99]
lurasidone Rn Antagonist 8.8 pKi 53
pKi 8.8 (Ki 1.68x10-9 M) [53]
olanzapine Hs Antagonist 8.7 pKi 10
pKi 8.7 (Ki 2.1x10-9 M) [10]
mesoridazine Hs Antagonist 8.7 pKi 31
pKi 8.7 (Ki 2.2x10-9 M) [31]
roxindole Hs Antagonist 8.6 pKi 81
pKi 8.6 [81]
ziprasidone Hs Antagonist 8.6 pKi 10
pKi 8.6 (Ki 2.8x10-9 M) [10]
nafadotride Hs Antagonist 8.5 pKi 98
pKi 8.5 [98]
raclopride Rn Antagonist 7.7 – 9.3 pKi 99,114
pKi 7.7 – 9.3 [99,114]
domperidone Rn Antagonist 8.5 pKi 114
pKi 8.5 [114]
sertindole Hs Antagonist 8.0 – 8.9 pKi 58-59,103
pKi 8.0 – 8.9 (Ki 9.1x10-9 – 1.2x10-9 M) [58-59,103]
prochlorperazine Hs Antagonist 8.4 pKi 12
pKi 8.4 (Ki 3.61x10-9 M) [12]
haloperidol Rn Antagonist 8.3 pKi 114
pKi 8.3 [114]
(+)-sulpiride Hs Antagonist 8.2 pKi 40
pKi 8.2 (Ki 6x10-9 M) [40]
L-741,626 Hs Antagonist 7.9 – 8.5 pKi 45,61
pKi 7.9 – 8.5 [45,61]
domperidone Hs Antagonist 7.9 – 8.4 pKi 40,112
pKi 7.9 – 8.4 (Ki 1.26x10-8 – 3.98x10-9 M) [40,112]
loxapine Hs Antagonist 7.9 – 8.3 pKi 59,105
pKi 7.9 – 8.3 (Ki 1.2x10-8 – 5x10-9 M) [59,105]
(+)-butaclamol Hs Antagonist 7.5 – 8.7 pKi 24,40,70,119
pKi 7.5 – 8.7 [24,40,70,119]
haloperidol Hs Antagonist 7.4 – 8.8 pKi 40,70,80,112,120
pKi 7.4 – 8.8 [40,70,80,112,120]
raclopride Hs Antagonist 8.0 pKi 82
pKi 8.0 (Ki 1x10-8 M) [82]
zotepine Hs Antagonist 8.0 pKi 102
pKi 8.0 (Ki 1.1x10-8 M) [102]
(-)-stepholidine Hs Antagonist 7.9 pKi 79
pKi 7.9 (Ki 1.16x10-8 M) [79]
pimozide Hs Antagonist 7.0 – 8.8 pKi 40,112
pKi 7.0 – 8.8 [40,112]
amisulpride Hs Antagonist 7.8 – 8.0 pKi 74,112,114
pKi 7.9 – 8.0 [74,112]
pKi 7.8 [114]
pimozide Rn Antagonist 7.6 pKi 114
pKi 7.6 [114]
sulpiride Hs Antagonist 7.2 – 7.9 pKi 24
pKi 7.2 – 7.9 (Ki 6x10-8 – 1.2x10-8 M) [24]
metoclopramide Mm Antagonist 7.5 pKi 76
pKi 7.5 (Ki 2.88x10-8 M) [76]
chlorpromazine Rn Antagonist 7.5 pKi 114
pKi 7.5 [114]
lumateperone Hs Antagonist 7.5 pKi 68,111
pKi 7.5 (Ki 3.2x10-8 M) [68,111]
chlorpromazine Hs Antagonist 7.0 – 7.6 pKi 40,112
pKi 7.0 – 7.6 [40,112]
quetiapine Hs Antagonist 7.2 pKi 10
pKi 7.2 (Ki 6.9x10-8 M) [10]
(-)-sulpiride Hs Antagonist 6.3 – 8.0 pKi 40,112,119
pKi 6.3 – 8.0 (Ki 5.2x10-7 – 1x10-8 M) [40,112,119]
(+)-sulpiride Rn Antagonist 7.0 pKi 114
pKi 7.0 [114]
ML321 Hs Antagonist 7.0 pKi 127-128
pKi 7.0 (Ki 1x10-7 M) [127-128]
trans-flupenthixol Hs Antagonist 6.9 pKi 40
pKi 6.9 (Ki 1.2x10-7 M) [40]
(+)-UH232 Hs Antagonist 6.4 – 7.1 pKi 40,114
pKi 6.4 – 7.1 [40,114]
promazine Hs Antagonist 6.5 pKi 25
pKi 6.5 (Ki 3x10-7 M) [25]
(+)-UH232 Rn Antagonist 6.4 pKi 114
pKi 6.4 [114]
clozapine Hs Antagonist 5.8 – 6.9 pKi 40,70,109,112,119
pKi 5.8 – 6.9 [40,70,109,112,119]
clozapine Rn Antagonist 6.2 pKi 114
pKi 6.2 [114]
(+)-S-14297 Hs Antagonist 5.5 pKi 82
pKi 5.5 [82]
(+)-SCH-23390 Hs Antagonist 5.3 pKi 40
pKi 5.3 [40]
iloperidone Rn Antagonist 7.0 pIC50 117
pIC50 7.0 (IC50 1.1x10-7 M) [117]
Description: Measuring displacement of [3H]spiperone from rat striatum.
View species-specific antagonist tables
Antagonist Comments
Terguride/roxindole have been reported to act as partial agonists at the D2S receptor and as antagonists at the D2L receptor.
Perphenazine is an antagonist at both the D2S and D2L receptors [118].
The approved drug mesoridazine, although consisting of 4 stereoisomers, appears to be selective for the D2 receptor [31], especially when examining the data for the two highest affinity isomers, compounds 2 and 5. Across the 3 dopamine receptors, compounds 2 and 5 have the same order of potency (D2>D3>D1). The data shown in the table above is for compound 2. Mesoridazine is also a selective antagonist of the serotonin 5-HT2A receptor.
Zotepine has a Ki of 5.4nM for the D2S receptor isoform [102].
The β-arrestin biased ligands UNC9975, UNC0006 and UNC9994, do not activate D2 receptor-mediated Gi-regulated inhibition of cAMP production, but rather are functionally-selective antagonists of the interaction between D2 receptor and β-arrestin-2 [3].
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
SB269652 Hs Negative 6.4 pKB 65
pKB 6.4 (KB 4.16x10-7 M) [65]
Description: Allosteric reduction of dopamine binding in a radioligand binding assay
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family
G protein independent mechanism
Adenylate cyclase inhibition
Other - See Comments
Comments:  Dopamine D2 receptors can inhibit the Akt (protein kinase B) pathway through a β-arrestin 2/Akt/protein phosphatase 2A complex [14-15].
D2L-induced inhibition of Akt is reported in pituitary lactotrophs, with D2S-induced ERK stimulation also reported in these cells [52,90].
References:  54,84,86
Secondary Transduction Mechanisms
Transducer Effector/Response
Potassium channel
Other - See Comments
Comments:  β-arrestin recruitment [39,79,127-128].
References:  30
Tissue Distribution
Pituitary, substantia nigra (SN) and ventral tegmental area (VTA).
Species:  Human
Technique:  In situ histochemistry.
References:  41,51
Adrenal cortex.
Species:  Human
Technique:  Autoradiography.
References:  4
Pityitary (autoradiography), substantia nigra (SN) and ventral tegmental area (VTA) (immunohistochemistry in BAC transgenics).
Species:  Mouse
Technique:  Autoradiography, immunohistochemistry.
References:  48,95
Prelimbic cortex.
Species:  Mouse
Technique:  Confocal analysis in the Bac-GFP reporter mouse.
References:  132
Hippocampus.
Species:  Mouse
Technique:  Bac-GFP reporter mouse.
References:  92
Cerebral, mesenteric and renal arteries.
Species:  Rat
Technique:  Autoradiography.
References:  5
Striatonigral neurons.
Species:  Rat
Technique:  Immunofluorescence.
References:  9
Striatum.
Species:  Rat
Technique:  In situ hybridization.
References:  26
Pituitary, substantia nigra (SN) and ventral tegmental area (VTA).
Species:  Rat
Technique:  In situ histochemistry.
References:  23
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 cAMP levels in GH4C1 cells transfected with the D2 receptor.
Species:  Rat
Tissue:  GH4C1 cells.
Response measured:  Inhibition of cAMP accumulation.
References:  2
Measurement of prolactin secretion in GH4C1 cells transfected with the D2 receptor.
Species:  Rat
Tissue:  GH4C1 cells.
Response measured:  Inhibition of prolactin secretion.
References:  2
Measurement of voltage-dependent potassium current in NG108-15 cells transfected witht the D2 receptor.
Species:  Rat
Tissue:  NG108-15 cells.
Response measured:  Inhibition of voltage-dependent potassium current.
References:  29
Measurement of activation of potassium channel in rat lactotrophs endogenously expressing the D2 receptor.
Species:  Rat
Tissue:  Lactotrophs.
Response measured:  Activation of potassium channel.
References:  30
Measurement of Ca2+ and cAMP levels in Ltk- cells transfected with both the long and short forms of the human D2 receptor.
Species:  Human
Tissue:  LTK- cells.
Response measured:  Stimulation of calcium mobilisation and cAMP accumulation.
References:  69
Measurement of [3H]thymidine incorporation in CHO cells transfected with the human D2 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  [3H]thymidine incorporation.
References:  64
Measurement of cAMP levels in CHO cells transfected with the human D2 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Inhibition of cAMP accumulation.
References:  64
Measurement of [3H]arachidonic acid release from rat striatal neurons endogenously expressing the D2 receptors.
Species:  Rat
Tissue:  Striatal neurons.
Response measured:  Enhanced [3H]arachidonic acid release.
References:  100
Measurement of cAMP levels in HEK 293 cells transfected with the human D2 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Inhibition of cAMP accumulation.
References:  77,126
Measurement of Cl- currents in Xenopus oocytes transfected with murine D2L and D2S receptors.
Species:  Mouse
Tissue:  Xenopus oocytes.
Response measured:  Stimulation of Cl- influx.
References:  110
Measurement of inwardly rectifying K+ currents in Xenopus oocytes transfected with the human D2 receptor.
Species:  Human
Tissue:  Xenopus oocytes.
Response measured:  Activation of GIRK1 channels.
References:  88
Measurement of inhibition of cAMP dependent transcription using murine D2L and D2S receptors.
Species:  Mouse
Tissue:  HEK293, COS and JEG3 cells.
Response measured: 
References:  84
Physiological Functions
Stimulation of accumulation of cAMP in membrane particles of the rat kidney medulla.
Species:  Human
Tissue:  Membrane particles of the rat kidney medulla.
References:  6
Inhibits Na+-K+-adenosinetriphosphatase (ATPase) activity when a D1 agonist is co-administered with a D2 agonist.
Species:  Rat
Tissue:  Proximal tubule.
References:  17
Inhibition of (Na+)+K+)ATPase activity via synergism with the D1 receptor.
Species:  Rat
Tissue:  Isolated striatal neurons.
References:  18
Control of renal blood flow.
Species:  Human
Tissue:  In vivo.
References:  22
Modulation of striatal dopamine.
Species:  Rat
Tissue:  In vivo.
References:  57
Reward effects of morphine.
Species:  Rat
Tissue:  In vivo.
References:  75
Blockade enhances learning/memory.
Species:  Rat
Tissue:  In vivo.
References:  108
Modulation of locomotor activity. (NB rat and mouse)
Species:  Rat
Tissue:  In vivo.
References:  21,116
Physiological Consequences of Altering Gene Expression
D2 receptor knockout mice exhibit a decrease in dopamine transporter (DAT) activity.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  35
D2 receptor knockout mice exhibit altered dopamine release and uptake.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  101
D2 receptor knockout mice display Parkinsonian-like locomotor impairment when compared to the wild type.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  13,38
D2 receptor knockout mice exhibit abnormal synaptic plasticity.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  28
D2 receptor knockout mice do not exhibit autoreceptor-mediated inhibitory control of dopamine release in striatal synaptosomes, as seen in wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  63
D2 receptor knockout mice exhibit d-amphetamine-induced disruption of prepulse inhibition, as seen in wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  91
D2 receptor knockout mice are insensitive to the hypolocomotor and hypothermic effects of D2/D3 agonists.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  20
D2 receptor knockout mice are insensitive to the cataleptic effects of haloperidol.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  19
D2 receptor knockout mice exhibit reduced ethanol-conditioned place preference.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  34
D2L receptor knockout mice exhibit reduced aggression.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  124
D2 receptor knockout mice do not exhibit autoinhibition of dopamine release.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  16,93
D2 receptor knockout mice exhibit increased rates of high-dose cocaine self-administration.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  27
D2 receptor knockout mice exhibit reduced locomotor activity and slower acquisition of a place-learning task.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  121
D2 receptor knockout mice exhibit altered GABAergic neurotransmission.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  7
D2L receptor knockout mice (which still express the short form of the receptor, D2S) exhibit reduced haloperidol-induced catalepsy.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  122,125
D2 receptor knockout mice exhibit hyperprolactinemia.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  11,20,55-56,94-95,129
D2 receptor knockout mice do not show place preference for morphine nor do they self administer the drug.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  37,73
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Drd2tm1Low Drd2tm1Low/Drd2tm1Low
either: B6.129S2-Drd2 or (involves: 129S2/SvPas * C57BL/6)
MGI:94924  MP:0004163 abnormal adenohypophysis morphology PMID: 9247267 
Drd2tm1Yyw