Affinage

DRD1

D(1A) dopamine receptor · UniProt P21728

Length
446 aa
Mass
49.3 kDa
Annotated
2026-04-28
100 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DRD1 encodes the dopamine D1 receptor, a Gαs-coupled GPCR that serves as a primary mediator of dopaminergic signaling in the brain and peripheral tissues, governing synaptic plasticity, motor learning, reward behavior, neural stem cell fate, and renal sodium homeostasis. Canonically, DRD1 signals through Gαs–cAMP–PKA to activate downstream effectors including mTORC1, ERK1/2 (via a D1R/Shp-2 complex), and CREB, and its cryo-EM structures reveal a polar agonist-recognition network and an allosteric inner-surface pocket that modulates orthosteric dopamine binding (PMID:33571432, PMID:26314207, PMID:23328768). DRD1 diversifies its signaling through heteromeric interactions: complexing with GHSR1a switches coupling to Gαq–PLC–Ca²⁺–CaMKII to drive hippocampal synaptic reorganization, complexing with GluN1 facilitates NMDAR calcium influx and striatal LTP, and heterodimerization with D5R in renal tubules cooperatively inhibits NHE3 and Na⁺/K⁺-ATPase via a PLC pathway (PMID:26590421, PMID:25070539, PMID:24552847). Constitutive DRD1 activity regulates human neural stem cell proliferation versus differentiation through a PKC–CBP pathway, and in lung endothelium DRD1 maintains barrier integrity via cAMP/EPAC-mediated HDAC6 inactivation (PMID:32052915, PMID:33456556).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2009 High

    Establishing post-transcriptional regulation of DRD1: miR-504 was shown to directly bind the DRD1 3′UTR and upregulate expression in an allele-specific manner at the rs686 polymorphism, revealing a previously unknown regulatory layer for receptor abundance.

    Evidence Luciferase reporter assays with site-directed mutagenesis of miR-504 binding site

    PMID:19135651

    Open questions at the time
    • Whether miR-504 regulation of DRD1 operates in vivo in neurons
    • Physiological consequences of allele-specific DRD1 expression differences
  2. 2010 High

    Demonstrating that DRD1 is required for hippocampal LTP and multiple forms of learning resolved whether D1-family signaling in hippocampus is necessary or merely modulatory for plasticity-dependent memory.

    Evidence Drd1a knockout mice and intrahippocampal siRNA knockdown with in vivo LTP recording and behavioral testing

    PMID:20844125

    Open questions at the time
    • Whether D1R acts cell-autonomously in CA1 pyramidal neurons or indirectly via interneurons
    • Downstream transcriptional program beyond Egr1
  3. 2011 High

    Cell-type specificity of NMDAR requirement in D1R neurons for psychostimulant sensitization established that the critical site of dopamine–glutamate integration is in D1R-expressing MSNs, not dopamine neurons.

    Evidence Conditional Grin1 deletion in D1R neurons with viral rescue and reinactivation in NAc

    PMID:21368124

    Open questions at the time
    • Molecular mechanism by which balanced D1R/D2R NMDAR loss permits sensitization
    • Which intracellular signaling cascades downstream of D1R-NMDAR interaction mediate plasticity
  4. 2013 High

    Identification of the D1R/Shp-2 complex as a causal upstream driver of ERK1/2 activation in L-DOPA-induced dyskinesia revealed a non-canonical signaling partner through which D1R engages the MAPK pathway in striatal neurons.

    Evidence Reciprocal co-immunoprecipitation of endogenous D1R and Shp-2 with pharmacological rescue in 6-OHDA rats

    PMID:23328768

    Open questions at the time
    • Structural basis of D1R–Shp-2 interaction
    • Whether Shp-2 engagement is constitutive or agonist-dependent
  5. 2014 High

    Discovery that D1R/GluN1 complexes form upon concomitant stimulation and are required for D1R-mediated NMDAR facilitation, striatal LTP, and cocaine sensitization provided a direct physical mechanism for dopamine–glutamate crosstalk in MSNs.

    Evidence Endogenous co-immunoprecipitation plus cell-permeable disrupting peptide with electrophysiology and behavioral readouts

    PMID:25070539

    Open questions at the time
    • Stoichiometry and structural interface of the D1R–GluN1 complex
    • Whether the complex involves additional scaffolding proteins
  6. 2014 High

    Demonstration that D1R and D5R form a functional heteromeric complex in renal proximal tubule cells that cooperatively inhibits sodium transport expanded DRD1 biology beyond the nervous system and revealed receptor-specific pathway segregation (cAMP vs. PLC).

    Evidence FRET microscopy, co-immunoprecipitation, real-time FRET biosensors for cAMP/PLC, siRNA knockdown, and sodium transport assays

    PMID:24552847

    Open questions at the time
    • In vivo renal phenotype of D1R/D5R heteromer disruption
    • Whether heteromerization alters receptor trafficking or desensitization
  7. 2015 High

    The GHSR1a–DRD1 heteromer was shown to switch D1R coupling from canonical Gαs to Gαq–PLC–Ca²⁺–CaMKII, establishing that receptor heterodimerization can fundamentally reprogram G protein selectivity of DRD1.

    Evidence Single-molecule imaging, FRET, co-immunoprecipitation, GHSR1a KO mice, and behavioral assays in hippocampal neurons

    PMID:26590421

    Open questions at the time
    • Whether GHSR1a–DRD1 heteromers exist in brain regions beyond hippocampus
    • Structural basis of G protein switching
  8. 2015 High

    DRD1 was placed upstream of mTORC1 activation in nucleus accumbens, establishing a D1R→PKA→mTOR signaling axis that mediates cocaine-induced locomotor responses.

    Evidence D1R knockout mice, D1R-selective pharmacology, conditional mTOR/Raptor deletion in D1R neurons

    PMID:26314207

    Open questions at the time
    • Direct biochemical link between PKA and mTORC1 activation in this context
    • Whether mTORC1 mediates D1R-dependent synaptic plasticity or primarily metabolic effects
  9. 2017 Medium

    DRD1→PKA→mTOR signaling was extended to the mPFC where it drives synaptogenesis-related protein expression and LTP, demonstrating this cascade operates across multiple brain regions for synaptic potentiation.

    Evidence Pharmacological pathway dissection with electrophysiology and western blotting in rat mPFC

    PMID:28630404

    Open questions at the time
    • Whether mPFC D1R–mTOR pathway is PKA-dependent or involves parallel routes
    • Cell-type specificity of this pathway within mPFC
  10. 2019 High

    Circuit-level studies using optogenetics and chemogenetics established that DRD1-expressing neurons in mPFC and NAc are causally required for specific behavioral outputs — rapid antidepressant action (mPFC D1R→BLA circuit), aggression seeking (NAc D1R neurons), and learned motor action initiation (DLS D1R neurons) — defining DRD1 as a cell-type marker for functionally distinct output pathways.

    Evidence Cell-type specific optogenetics and DREADD chemogenetics in Drd1-Cre mice with behavioral readouts across multiple labs

    PMID:30644390 PMID:30655356 PMID:31072930

    Open questions at the time
    • Whether DRD1 signaling itself or simply D1R neuron identity drives these behaviors
    • Molecular mechanisms downstream of D1R activation in each circuit
  11. 2019 Medium

    β-arrestin2 was identified as a negative regulator of D1R signaling in L-DOPA-induced dyskinesia, providing a desensitization mechanism that modulates the D1R/Shp-2/ERK pathway.

    Evidence Bidirectional AAV-mediated β-arrestin2 manipulation with pharmacological D1R rescue in 6-OHDA rats

    PMID:31891566

    Open questions at the time
    • Whether β-arrestin2 acts by receptor internalization or signaling scaffold disruption
    • Relationship to biased agonism at D1R
  12. 2020 High

    Constitutive (agonist-independent) DRD1 activity was shown to regulate human neural stem cell proliferation versus differentiation via PKC–CBP, revealing a developmental role for D1R independent of dopamine.

    Evidence Inverse agonist pharmacology, CRISPR knock-in of A229T reduced-activity mutant, human cerebral organoid cortical folding assay

    PMID:32052915

    Open questions at the time
    • Endogenous ligand-independent signaling levels in developing human cortex in vivo
    • Whether PKC–CBP pathway intersects with canonical Gαs–cAMP signaling
  13. 2021 High

    Cryo-EM structures of DRD1–Gs complexes resolved the molecular basis of agonist recognition, D1/D2 selectivity, and positive allosteric modulation, providing the first atomic-level framework for DRD1 pharmacology.

    Evidence Five cryo-EM structures with catechol/non-catechol agonists and allosteric modulator

    PMID:33571432

    Open questions at the time
    • Structures with antagonists or inverse agonists
    • Structural basis of heteromer-induced G protein switching
  14. 2021 High

    DRD1 was identified as a regulator of endothelial barrier integrity: D1R activation maintains α-tubulin acetylation via cAMP/EPAC-mediated HDAC6 inactivation, and D1R loss exacerbates mechanical stretch-induced lung injury.

    Evidence DRD1 knockout mice, cell-specific knockdown, pharmacological agonism in lung vascular endothelial cells

    PMID:33456556

    Open questions at the time
    • Whether this pathway operates in other vascular beds
    • Upstream mechanism of D1R downregulation during mechanical stretch
  15. 2023 High

    DRD1 activation was shown to promote TrkB surface trafficking and BDNF sensitivity in direct-pathway striatal neurons, linking dopamine depletion in Parkinson's disease to impaired neurotrophic signaling via intracellular TrkB sequestration with SORCS-2.

    Evidence FACS-enriched D1R-SPN cultures, 6-OHDA rat model, postmortem human PD brain, co-immunoprecipitation

    PMID:37252844

    Open questions at the time
    • Mechanism by which D1R signaling promotes TrkB externalization
    • Whether SORCS-2 sequestration is protective or pathological

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of DRD1 heteromeric complexes (with GHSR1a, D5R, GluN1), the mechanism of constitutive activity in neural stem cells at the structural level, and whether D1R-intrinsic signaling versus D1R-neuron identity drives circuit-level behavioral phenotypes.
  • No structures of DRD1 heteromeric complexes
  • No reconstitution of heteromer-dependent G protein switching
  • Cell-autonomous versus circuit-level contributions of D1R signaling in behavior remain conflated in most studies

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-162582 Signal Transduction 8 R-HSA-112316 Neuronal System 6 R-HSA-1266738 Developmental Biology 1
Partners
ARRB2DRD2DRD5GHSRGRIN1NEFMPTPN11
Complex memberships
DRD1-DRD2 heterodimerDRD1-DRD5 heteromerDRD1-GluN1 complexGHSR1a-DRD1 heteromer

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2021 Cryo-EM structures of DRD1 coupled to Gs heterotrimer revealed that a polar interaction network is essential for catecholamine-like agonist recognition, specific motifs in an extended binding pocket discriminate D1- from D2-like receptors, and allosteric binding at a distinct inner surface pocket stabilizes endogenous dopamine at the orthosteric site to enhance DRD1 activity. Key features of the DRD1-Gs interface were identified as determinants for G protein coupling. Cryo-electron microscopy (cryo-EM) with five distinct structures including catechol-based agonists, non-catechol agonist, and positive allosteric modulator Cell High 33571432
2015 GHSR1a (ghrelin receptor) and DRD1 form a heteromeric complex in hippocampal neurons, demonstrated by real-time single-molecule analysis and proximity measurements. DRD1 agonism drives non-canonical Gαq-PLC-IP3-Ca2+ signaling (instead of canonical Gαs-cAMP) through the preassembled GHSR1a:DRD1:Gαq complex, leading to CaMKII activation, glutamate receptor exocytosis, and synaptic reorganization. Genetic or pharmacological inactivation of GHSR1a blocks this DRD1-dependent hippocampal plasticity pathway. Real-time single-molecule imaging, FRET proximity measurements, co-immunoprecipitation, pharmacological and genetic inactivation of GHSR1a, behavioral assays Cell High 26590421
2014 Concomitant stimulation of D1R and NMDAR drives formation of endogenous D1R/GluN1 (NMDAR) complexes in striatal medium spiny neurons. Preventing D1R/GluN1 association with a cell-permeable peptide (TAT-GluN1C1) leaves individual receptor signaling intact but blocks D1R-mediated facilitation of NMDAR-calcium influx and ERK activation, impairs long-term potentiation at D1R-MSN synapses, and reduces cocaine behavioral sensitization. Co-immunoprecipitation of endogenous proteins, cell-permeable peptide disruption, electrophysiology in striatal slices, in vivo intra-striatal peptide delivery, behavioral sensitization assay Molecular psychiatry High 25070539
2013 DRD1 physically interacts with Shp-2 (an intracellular tyrosine phosphatase) in striatal neurons, forming a D1R/Shp-2 complex. Activation of this complex by D1R agonists or L-DOPA leads to Shp-2 phosphorylation and downstream ERK1/2 activation, which is persistently elevated in L-DOPA-induced dyskinesia (LID). D1R antagonist SCH23390 prevents both dyskinesia and Shp-2/ERK1/2 activation, establishing D1R/Shp-2 as a causal upstream component of LID. Co-immunoprecipitation, western blotting (phospho-Shp-2, phospho-ERK1/2), pharmacological manipulation with D1R agonist/antagonist, 6-OHDA rat model of Parkinson's disease Neurobiology of disease High 23328768
2015 Cocaine-induced increases in mTORC1 activity (phosphorylation of mTOR at Thr2446 and Ser2481, and downstream 4E-BP1 and S6K) in the nucleus accumbens are mediated specifically through DRD1: blocked by D1R antagonist SCH23390 but not D2R antagonist raclopride, absent in D1R knockout mice, and recapitulated by D1R agonist SKF81297. Deletion of mTOR or Raptor in D1R-expressing neurons reduced cocaine-induced locomotor activity. Pharmacological blockade, D1R knockout mice, D1R agonist administration, conditional knockout of mTOR/Raptor in D1R neurons, western blotting for phospho-mTOR complexes Neuropharmacology High 26314207
2014 D1R and D5R colocalize in renal proximal tubule cells and physically interact as shown by co-immunoprecipitation and FRET microscopy. D1R stimulation primarily activates adenylyl cyclase (cAMP), while a D1R/D5R heteromer modulates signaling through a PLC pathway. Both pathways cooperatively inhibit NHE3 and Na/K-ATPase sodium transport; D1R siRNA blocks both cAMP and PLC signaling, whereas D5R siRNA or selective D5R antagonist blocks only the PLC pathway. Co-immunoprecipitation, FRET microscopy, real-time FRET biosensors (ICUE3, CYPHR) for cAMP and PLC, siRNA gene silencing, selective pharmacological antagonists, functional sodium transport assays Kidney international High 24552847
2023 DRD1 activation in direct pathway striatal medium spiny neurons (dSPNs) causes enhanced translocation of TrkB (BDNF receptor) to the cell surface and increased sensitivity to BDNF. Dopamine depletion (in cultured neurons, 6-OHDA rats, and postmortem Parkinson's disease brain) reduces BDNF responsiveness and causes formation of intracellular TrkB clusters that associate with SORCS-2 in multivesicular-like structures, apparently protecting TrkB from lysosomal degradation. FACS-enriched D1R-expressing SPN cultures, 6-OHDA rat model, postmortem human PD brain analysis, western blotting, immunofluorescence, co-immunoprecipitation Cell reports High 37252844
2020 DRD1 has high constitutive (agonist-independent) activity in human neural stem cells. Inhibition of DRD1 constitutive activity by inverse agonists, or genetic knockdown/knock-in of a reduced-activity A229T mutant (via CRISPR-Cas9), promotes NSC proliferation and impedes differentiation. In human cerebral organoids, reducing DRD1 constitutive activity expands NSCs and promotes cortical folding. The PKC-CBP pathway mediates these effects. Inverse agonist pharmacology, siRNA knockdown, CRISPR-Cas9 knock-in of A229T loss-of-function mutant, human cerebral organoid assay, pathway inhibitor studies (PKC-CBP) Stem cells High 32052915
2021 DRD1 downregulation in lung vascular endothelial cells during mechanical stretch leads to HDAC6-mediated α-tubulin deacetylation and endothelial hyperpermeability. DRD1 activation attenuates mechanical stretch-induced endothelial barrier dysfunction via a cAMP/EPAC-mediated inactivation of HDAC6 pathway. DRD1 knockout mice show exacerbated mechanical stretch-induced lung injury. DRD1 knockout mice, pulmonary knockdown, isolated mouse lung vascular endothelial cells, pharmacological DRD1 agonist treatment, western blotting for phospho-GSK-3β, phospho-HDAC6, acetylated α-tubulin Theranostics High 33456556
2009 miR-504 upregulates DRD1 expression by directly binding to the DRD1 3'UTR, and this interaction is allele-specific at the rs686 polymorphism. Site-directed mutagenesis of the miR-504 binding site abolished the differential allelic expression, establishing miR-504 as a regulator of DRD1 through its 3'UTR. Luciferase reporter assay, site-directed mutagenesis, miRNA inhibitor experiments, gene expression assay Biological psychiatry High 19135651
2014 BDNF-TrkB signaling in D1R-expressing NAc MSNs selectively modulates GABAergic activity: TrkB knockout from D1R-MSNs decreases GABAA receptor subunit expression and reduces spontaneous inhibitory postsynaptic currents (sIPSCs) specifically in D1-type MSNs. This reduction of GABA inhibition in D1R-MSNs enhances morphine reward. Optical activation of D1R-MSNs also enhances morphine reward. Cell-type specific TrkB conditional knockout (D1-TrkB KO), optogenetics, whole-cell electrophysiology (sIPSC recordings), western blotting for GABAAR subunits, conditioned place preference assay Neuropsychopharmacology High 24853771
2017 NEFM (neurofilament medium polypeptide) co-immunoprecipitates with DRD1 and acts as a negative regulator of D1R-mediated aldosterone secretion. NEFM silencing amplifies DRD1 agonist (fenoldopam)-stimulated aldosterone production and is associated with intracellular DRD1 localization in zona glomerulosa-like cells, suggesting NEFM facilitates DRD1 internalization from the plasma membrane. Co-immunoprecipitation (DRD1-NEFM), siRNA silencing of NEFM, aldosterone secretion assays, immunohistochemistry for DRD1 subcellular localization Hypertension Medium 28584012
2017 In the mPFC, DRD1 activation triggers a D1R/PKA/mTOR signaling cascade that increases synaptogenesis-related proteins (PSD-95, synapsin I) and induces LTP. L-SPD acts as a D1R agonist in the mPFC, and its antidepressant effects are blocked by D1R, PKA, or mTOR inhibitors, establishing D1R→PKA→mTOR as a mechanistic pathway for mPFC synaptic potentiation. Pharmacological agonism/antagonism (l-SPD, SCH23390, PKA inhibitor, rapamycin), LTP electrophysiology, western blotting for PSD-95, synapsin I, phospho-PKA substrates, rat CMS depression model Scientific reports Medium 28630404
2022 Using fluorescent protein-based multicolor biosensors monitoring individual DRD1 and DRD2 activation states in live cells, DRD1-DRD2 heterodimers show differential receptor crosstalk depending on dopamine concentration: DRD1 activation is selectively inhibited at micromolar (phasic) dopamine levels, while DRD2 is inhibited by nanomolar (tonic) dopamine, revealing a novel concentration-dependent functional regulation of the DRD1-DRD2 heterodimer. Fluorescent protein-based multicolor GPCR biosensors in live cells, pharmacological manipulation with different dopamine concentrations Progress in neurobiology Medium 35364139
2011 NMDAR signaling specifically in D1R-expressing striatal MSNs (not dopamine neurons) is required for amphetamine behavioral sensitization. Conditional deletion of NR1 (Grin1) from D1R neurons significantly attenuated sensitization, while virus-mediated restoration of NR1 in D1R neurons in the NAc rescued it. Balanced loss of NMDARs from both D1R and D2R-expressing MSNs is permissive for sensitization, whereas unbalanced loss from D1R-MSNs alone prevents it. Cell-type specific conditional knockout (Grin1 deletion in D1R neurons), viral-mediated NR1 restoration, viral-mediated NR1 inactivation, behavioral sensitization assay PNAS High 21368124
2017 Gastric bypass (RYGB) surgery upregulates striatal DRD1 expression specifically under high-fat diet feeding conditions. Interfering with striatal D1R signaling negated the RYGB-induced reduction of fat intake, placing striatal DRD1 as a downstream effector in a gut PPAR-α → vagus nerve → dorsal striatal dopamine release circuit that reduces fat appetite after RYGB. Pharmacological blockade of D1R, RYGB surgery in rats, striatal dopamine measurement, DRD1 expression analysis, vagal nerve manipulation Cell metabolism Medium 28065827
2010 D1R (Drd1a) is required for associative learning, spatial learning, and fear learning. D1R knockout mice and hippocampal siRNA knockdown of Drd1a both impair CA3-CA1 synaptic LTP in behaving mice and reduce Egr1 induction following LTP, establishing a functional relationship between D1R expression, hippocampal synaptic plasticity, and associative learning. Drd1a knockout mice, intrahippocampal siRNA injection, in vivo LTP recording, conditioned eyeblink response, Morris water maze, fear conditioning, Egr1 immunohistochemistry Journal of Neuroscience High 20844125
2024 In aged 5xFAD Alzheimer's disease model mice, the dopamine analogue CA140 improves synaptic/cognitive function through DRD1/Elk1 signaling. In primary hippocampal neurons, CA140 promotes dendritic spine formation and long-term memory via DRD1/CaMKIIα and/or ERK signaling, as established by pharmacological blockade of DRD1. DRD1 pharmacological antagonism, western blotting for DRD1 pathway components (Elk1, CaMKIIα, ERK), Golgi staining for dendritic spines, electrophysiology (LTP), behavioral memory tests in WT and 5xFAD mice Journal of neuroinflammation Medium 39129007
2019 Optogenetic stimulation of mPFC Drd1-expressing pyramidal neurons produces rapid and long-lasting antidepressant and anxiolytic effects, while Drd2-expressing neurons are ineffective. Disruption of Drd1 activity blocked ketamine's rapid antidepressant effects. Stimulation of mPFC Drd1 terminals specifically in the BLA recapitulates the antidepressant response, defining a mPFC Drd1→BLA circuit for rapid antidepressant action. Optogenetics (ChR2), cell-type specific expression in Drd1 vs Drd2 neurons, behavioral tests (sucrose preference, forced swim, EPM), terminal-specific optogenetic stimulation in BLA, pharmacological Drd1 disruption Nature communications High 30644390
2019 Chemogenetic inhibition (hM4Di DREADD) of NAc Drd1-expressing neurons, but not Drd2-expressing neurons, selectively decreases both aggression self-administration and aggression seeking in mice. Fos immunohistochemistry and in situ hybridization showed that aggression self-administration activates NAc neurons co-expressing Fos and Drd1. Cre-DREADD chemogenetic inhibition in Drd1-Cre and Drd2-Cre mice, Fos immunohistochemistry, fluorescent in situ hybridization, operant aggression self-administration paradigm Journal of Neuroscience High 30655356
2019 Long-term two-photon calcium imaging during motor learning revealed that D1R-expressing DLS neurons form stable ensembles that fire sequentially during learned motor behavior—D1R neurons fire predominantly during lever-pushing while D2R neurons fire during intertrial intervals. Selective chemogenetic silencing of D1R neurons impaired initiation of learned motor actions. Two-photon calcium imaging in D1R and D2R transgenic mice, chemogenetic silencing (DREADD), cued lever-pushing motor learning task PNAS High 31072930
2019 β-arrestin2 overexpression attenuates L-DOPA-induced dyskinesia (LID) in 6-OHDA rats by suppressing D1R signaling; this anti-dyskinetic effect is reversed by D1R agonist SKF38393. Conversely, β-arrestin2 knockdown worsens LID, which is counteracted by D1R antagonist SCH23390. This establishes that β-arrestin2 acts as a negative regulator of D1R-mediated LID signaling. AAV-mediated β-arrestin2 overexpression and knockdown, pharmacological D1R agonist and antagonist, AIMs behavioral assay, western blotting in 6-OHDA rat model Aging Medium 31891566
2015 Activation of DRD1 in breast cancer cells signals through the cGMP/protein kinase G (PKG) pathway to suppress cell viability, inhibit invasion, and induce apoptosis. In vivo, the peripheral DRD1 agonist fenoldopam dramatically suppressed tumor growth in mouse xenograft models expressing DRD1. DRD1 agonist treatment (dopamine, fenoldopam) in multiple breast cancer cell lines, cGMP/PKG pathway inhibitors, mouse xenograft models, cell viability/apoptosis/invasion assays Oncogene Medium 26477316
2024 DRD1 contributes to glioblastoma invasion and stemness by regulating c-Myc nuclear entry, which controls transcription of UHRF1. ChIP experiments confirmed c-Myc binding to the UHRF1 promoter. DRD1 knockdown or DRD1 antagonist SKF83566 reduced tumor growth in orthotopic xenografts, placing DRD1 upstream of a c-Myc-UHRF1 axis in GBM. RNA sequencing, ChIP assay (c-Myc at UHRF1 promoter), DRD1 knockdown and overexpression, pharmacological DRD1 inhibition (SKF83566), orthotopic xenograft mouse model Journal of experimental & clinical cancer research Medium 38246990
2022 Per2 knockout mice show elevated DRD1, PKA, and CREB expression in the hippocampus and impaired spatial working memory. Administration of D1R antagonist SCH-23390 to Per2 KO mice restores memory performance and reduces PKA and CREB levels, establishing that excessive DRD1-PKA-CREB signaling mediates the cognitive impairment in Per2-deficient mice. Per2 knockout mice, D1R antagonist administration, Barnes maze and Y-maze behavioral tests, western blotting for DRD1/PKA/CREB Molecular neurobiology Medium 35508866

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Involvement of putative SNF2 chromatin remodeling protein DRD1 in RNA-directed DNA methylation. Current biology : CB 233 15120073
2019 Optogenetic stimulation of medial prefrontal cortex Drd1 neurons produces rapid and long-lasting antidepressant effects. Nature communications 185 30644390
2006 RNAi, DRD1, and histone methylation actively target developmentally important non-CG DNA methylation in arabidopsis. PLoS genetics 169 16741558
2005 Support for association between ADHD and two candidate genes: NET1 and DRD1. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 159 15717291
2011 Differential regulation of motor control and response to dopaminergic drugs by D1R and D2R neurons in distinct dorsal striatum subregions. The EMBO journal 158 22068054
2021 Ligand recognition and allosteric regulation of DRD1-Gs signaling complexes. Cell 129 33571432
2010 Associative learning and CA3-CA1 synaptic plasticity are impaired in D1R null, Drd1a-/- mice and in hippocampal siRNA silenced Drd1a mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 115 20844125
2017 Gastric Bypass Surgery Recruits a Gut PPAR-α-Striatal D1R Pathway to Reduce Fat Appetite in Obese Rats. Cell metabolism 106 28065827
2015 Hippocampal Dopamine/DRD1 Signaling Dependent on the Ghrelin Receptor. Cell 100 26590421
2007 RNA-directed DNA methylation mediated by DRD1 and Pol IVb: a versatile pathway for transcriptional gene silencing in plants. Biochimica et biophysica acta 97 17449119
2009 Differential allelic expression of dopamine D1 receptor gene (DRD1) is modulated by microRNA miR-504. Biological psychiatry 95 19135651
2013 Contrasting changes in DRD1 and DRD2 splice variant expression in schizophrenia and affective disorders, and associations with SNPs in postmortem brain. Molecular psychiatry 90 24322206
2007 Significant association of DRD1 with nicotine dependence. Human genetics 89 18092181
2006 Immunohistochemical localization of dopamine receptor subtypes (D1R-D5R) in Alzheimer's disease brain. Brain research 89 17182012
2013 Spatial distribution of D1R- and D2R-expressing medium-sized spiny neurons differs along the rostro-caudal axis of the mouse dorsal striatum. Frontiers in neural circuits 88 23908605
2014 Loss of BDNF signaling in D1R-expressing NAc neurons enhances morphine reward by reducing GABA inhibition. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 82 24853771
2019 Nucleus Accumbens Drd1-Expressing Neurons Control Aggression Self-Administration and Aggression Seeking in Mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 76 30655356
2018 Exercise Reduces Dopamine D1R and Increases D2R in Rats: Implications for Addiction. Medicine and science in sports and exercise 76 29613999
2019 Emergence of stable striatal D1R and D2R neuronal ensembles with distinct firing sequence during motor learning. Proceedings of the National Academy of Sciences of the United States of America 71 31072930
2015 Expression and therapeutic targeting of dopamine receptor-1 (D1R) in breast cancer. Oncogene 71 26477316
2019 Which Dopamine Polymorphisms Are Functional? Systematic Review and Meta-analysis of COMT, DAT, DBH, DDC, DRD1-5, MAOA, MAOB, TH, VMAT1, and VMAT2. Biological psychiatry 69 31303260
2008 A DRD1 haplotype is associated with risk for autism spectrum disorders in male-only affected sib-pair families. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 69 18205172
2014 Differential roles of the dopamine 1-class receptors, D1R and D5R, in hippocampal dependent memory. Proceedings of the National Academy of Sciences of the United States of America 67 24843151
2013 Optogenetic inhibition of D1R containing nucleus accumbens neurons alters cocaine-mediated regulation of Tiam1. Frontiers in molecular neuroscience 66 23745104
2014 D1R/GluN1 complexes in the striatum integrate dopamine and glutamate signalling to control synaptic plasticity and cocaine-induced responses. Molecular psychiatry 65 25070539
2014 DRD1 and DRD2 genotypes modulate processing modes of goal activation processes during action cascading. The Journal of neuroscience : the official journal of the Society for Neuroscience 62 24719111
2008 A haplotype of the DRD1 gene is associated with alcohol dependence. Alcoholism, clinical and experimental research 61 18341651
1996 Systematic screening for mutations in the 5'-regulatory region of the human dopamine D1 receptor (DRD1) gene in patients with schizophrenia and bipolar affective disorder. American journal of medical genetics 59 8837716
2011 Balanced NMDA receptor activity in dopamine D1 receptor (D1R)- and D2R-expressing medium spiny neurons is required for amphetamine sensitization. Proceedings of the National Academy of Sciences of the United States of America 56 21368124
2017 Validation of dopamine receptor DRD1 and DRD2 antibodies using receptor deficient mice. Amino acids 54 28316027
2008 Blood pressure and renal sodium handling in relation to genetic variation in the DRD1 promoter and GRK4. Hypertension (Dallas, Tex. : 1979) 50 18413491
2010 Systematic analysis of dopamine receptor genes (DRD1-DRD5) in antipsychotic-induced weight gain. The pharmacogenomics journal 49 20714340
2014 Cannabinoid, melanocortin and opioid receptor expression on DRD1 and DRD2 subpopulations in rat striatum. Frontiers in neuroanatomy 47 24723856
2007 5' UTR polymorphism of dopamine receptor D1 (DRD1) associated with severity and temperament of alcoholism. Biochemical and biophysical research communications 45 17466946
2007 Polymorphisms in dopamine receptor DRD1 and DRD2 genes and psychopathological and extrapyramidal symptoms in patients on long-term antipsychotic treatment. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 37 17455212
2013 Persistent activation of the D1R/Shp-2/Erk1/2 pathway in l-DOPA-induced dyskinesia in the 6-hydroxy-dopamine rat model of Parkinson's disease. Neurobiology of disease 35 23328768
2002 Linkage disequilibrium between dopamine D1 receptor gene (DRD1) and bipolar disorder. Biological psychiatry 34 12488059
2013 The expression of MC4Rs in D1R neurons regulates food intake and locomotor sensitization to cocaine. Genes, brain, and behavior 33 23786641
2021 Optogenetic activation of striatal D1R and D2R cells differentially engages downstream connected areas beyond the basal ganglia. Cell reports 29 34965430
2019 Regulation of defeat-induced social avoidance by medial amygdala DRD1 in male and female prairie voles. Psychoneuroendocrinology 28 31862611
2015 Essential role of D1R in the regulation of mTOR complex1 signaling induced by cocaine. Neuropharmacology 28 26314207
2007 Human cytotoxic CD4+ T cells recognize HLA-DR1-restricted epitopes on vaccinia virus proteins A24R and D1R conserved among poxviruses. Journal of immunology (Baltimore, Md. : 1950) 28 17617623
2016 A Mutation in Plant-Specific SWI2/SNF2-Like Chromatin-Remodeling Proteins, DRD1 and DDM1, Delays Leaf Senescence in Arabidopsis thaliana. PloS one 27 26752684
2014 Dopamine receptor gene (DRD1-DRD5) expression changes as stress factors associated with breast cancer. Asian Pacific journal of cancer prevention : APJCP 27 25556472
2012 DRD1 rs4532 polymorphism: a potential pharmacogenomic marker for treatment response to antipsychotic drugs. Schizophrenia research 27 23036699
2007 Association of the dopamine receptor D1 gene, DRD1, with inattention symptoms in families selected for reading problems. Molecular psychiatry 27 17310237
2021 DRD1 and DRD2 Receptor Polymorphisms: Genetic Neuromodulation of the Dopaminergic System as a Risk Factor for ASD, ADHD and ASD/ADHD Overlap. Frontiers in neuroscience 26 34658761
2017 Activation of D1R/PKA/mTOR signaling cascade in medial prefrontal cortex underlying the antidepressant effects of l-SPD. Scientific reports 26 28630404
2017 Extinction of Contextual Cocaine Memories Requires Cav1.2 within D1R-Expressing Cells and Recruits Hippocampal Cav1.2-Dependent Signaling Mechanisms. The Journal of neuroscience : the official journal of the Society for Neuroscience 26 29089442
2014 The cooperative roles of the dopamine receptors, D1R and D5R, on the regulation of renal sodium transport. Kidney international 26 24552847
2014 Behavioral responses to pups in males with different reproductive experiences are associated with changes in central OT, TH and OTR, D1R, D2R mRNA expression in mandarin voles. Hormones and behavior 25 25496756
2020 Constitutive activity of a G protein-coupled receptor, DRD1, contributes to human cerebral organoid formation. Stem cells (Dayton, Ohio) 24 32052915
2014 A DRD1 polymorphism predisposes to lung cancer among those exposed to secondhand smoke during childhood. Cancer prevention research (Philadelphia, Pa.) 24 25281486
2013 Buspirone anti-dyskinetic effect is correlated with temporal normalization of dysregulated striatal DRD1 signalling in L-DOPA-treated rats. Neuropharmacology 24 24333147
2010 Sexually dimorphic interaction between the DRD1 and COMT genes in schizophrenia. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 24 20127886
2004 Ethnic origin determines the impact of genetic variants in dopamine receptor gene (DRD1) concerning essential hypertension. American journal of hypertension 23 15607627
2022 Dopamine D1R Receptor Stimulation as a Mechanistic Pro-cognitive Target for Schizophrenia. Schizophrenia bulletin 22 34423843
2020 Dopamine D1R-neuron cacna1c deficiency: a new model of extinction therapy-resistant post-traumatic stress. Molecular psychiatry 22 32332995
2019 GPR88 in D1R-Type and D2R-Type Medium Spiny Neurons Differentially Regulates Affective and Motor Behavior. eNeuro 22 31346000
2018 Transcriptomic context of DRD1 is associated with prefrontal activity and behavior during working memory. Proceedings of the National Academy of Sciences of the United States of America 22 29735686
2014 Acute sleep deprivation enhances avoidance learning and spatial memory and induces delayed alterations in neurochemical expression of GR, TH, DRD1, pCREB and Ki67 in rats. Behavioural brain research 22 25433096
2021 DRD1 downregulation contributes to mechanical stretch-induced lung endothelial barrier dysfunction. Theranostics 21 33456556
2017 NEFM (Neurofilament Medium) Polypeptide, a Marker for Zona Glomerulosa Cells in Human Adrenal, Inhibits D1R (Dopamine D1 Receptor)-Mediated Secretion of Aldosterone. Hypertension (Dallas, Tex. : 1979) 21 28584012
2015 Commonly-occurring polymorphisms in the COMT, DRD1 and DRD2 genes influence different aspects of motor sequence learning in humans. Neurobiology of learning and memory 21 26419600
2020 Fluoride Affects Dopamine Metabolism and Causes Changes in the Expression of Dopamine Receptors (D1R and D2R) in Chosen Brain Structures of Morphine-Dependent Rats. International journal of molecular sciences 20 32235357
2015 Differentiation of forebrain and hippocampal dopamine 1-class receptors, D1R and D5R, in spatial learning and memory. Hippocampus 20 26174222
2013 HIV-related cognitive impairment shows bi-directional association with dopamine receptor DRD1 and DRD2 polymorphisms in substance-dependent and substance-independent populations. Journal of neurovirology 20 24078558
2023 DRD1 signaling modulates TrkB turnover and BDNF sensitivity in direct pathway striatal medium spiny neurons. Cell reports 19 37252844
2021 D1R- and D2R-Medium-Sized Spiny Neurons Diversity: Insights Into Striatal Vulnerability to Huntington's Disease Mutation. Frontiers in cellular neuroscience 19 33642998
2019 Morphine Differentially Alters the Synaptic and Intrinsic Properties of D1R- and D2R-Expressing Medium Spiny Neurons in the Nucleus Accumbens. Frontiers in synaptic neuroscience 19 31920618
2010 Analysis of genetic variations in the dopamine D1 receptor (DRD1) gene and antipsychotics-induced tardive dyskinesia in schizophrenia. European journal of clinical pharmacology 19 21181138
2015 Association between GRK4 and DRD1 gene polymorphisms and hypertension: a meta-analysis. Clinical interventions in aging 17 26730182
2004 The Detection of Dopamine Gene Receptors (DRD1-DRD5) Expression on Human Peripheral Blood Lymphocytes by Real Time PCR. Iranian journal of allergy, asthma, and immunology 17 17301410
2018 Genetic Knockdown of mGluR5 in Striatal D1R-Containing Neurons Attenuates L-DOPA-Induced Dyskinesia in Aphakia Mice. Molecular neurobiology 16 30259400
2014 Dopaminergic tone persistently regulates voltage-gated ion current densities through the D1R-PKA axis, RNA polymerase II transcription, RNAi, mTORC1, and translation. Frontiers in cellular neuroscience 16 24596543
2009 Dopamine D1 receptor (DRD1) genetic polymorphism: pleiotropic effects on heritable renal traits. Kidney international 16 19675531
2024 The dopamine analogue CA140 alleviates AD pathology, neuroinflammation, and rescues synaptic/cognitive functions by modulating DRD1 signaling or directly binding to Abeta. Journal of neuroinflammation 14 39129007
2023 Selective Activation of NAc D1R-VP/LH Circuits Promotes Reanimation From Sevoflurane Anesthesia in Mice. Anesthesia and analgesia 14 36944111
2015 The Addiction-Related Gene Ankk1 is Oppositely Regulated by D1R- and D2R-Like Dopamine Receptors. Neurotoxicity research 14 26194616
2012 Molecular insights into the D1R agonist and D2R/D3R antagonist effects of the natural product (-)-stepholidine: molecular modeling and dynamics simulations. The journal of physical chemistry. B 14 22702398
2021 Serum miR-195-5p Exhibits Clinical Significance in the Diagnosis of Essential Hypertension with Type 2 Diabetes Mellitus by Targeting DRD1. Clinics (Sao Paulo, Brazil) 13 34495077
2019 β-arrestin2 alleviates L-dopa-induced dyskinesia via lower D1R activity in Parkinson's rats. Aging 13 31891566
2015 Age-related hypertension and salt sensitivity are associated with unique cortico-medullary distribution of D1R, AT1R, and NADPH-oxidase in FBN rats. Clinical and experimental hypertension (New York, N.Y. : 1993) 13 25562528
2023 Increased Excitability and Synaptic Plasticity of Drd1- and Drd2-Expressing Prelimbic Neurons Projecting to Nucleus Accumbens after Heroin Abstinence Are Reversed by Cue-Induced Relapse and Protein Kinase A Inhibition. The Journal of neuroscience : the official journal of the Society for Neuroscience 12 37094933
2022 Visualization of differential GPCR crosstalk in DRD1-DRD2 heterodimer upon different dopamine levels. Progress in neurobiology 12 35364139
2022 Per2 Expression Regulates the Spatial Working Memory of Mice through DRD1-PKA-CREB Signaling. Molecular neurobiology 12 35508866
2021 DRD1 agonist A-68930 improves mitochondrial dysfunction and cognitive deficits in a streptozotocin-induced mouse model. Brain research bulletin 12 34284074
2021 L-3,4-Dihydroxyphenylalanine Recovers Circadian Rhythm Disturbances in the Rat Models of Parkinson's Disease by Regulating the D1R-ERK1/2-mTOR Pathway. Frontiers in aging neuroscience 12 34489685
2017 Levodopa/Benserazide Loaded Microspheres Alleviate L-dopa Induced Dyskinesia through Preventing the Over-Expression of D1R/Shp-2/ERK1/2 Signaling Pathway in a Rat Model of Parkinson's Disease. Frontiers in aging neuroscience 12 29093677
2009 DRD1 5'UTR variation, sex and early infant stress influence ethanol consumption in rhesus macaques. Genes, brain, and behavior 12 19563515
2024 The dopamine receptor D1 inhibitor, SKF83566, suppresses GBM stemness and invasion through the DRD1-c-Myc-UHRF1 interactions. Journal of experimental & clinical cancer research : CR 11 38246990
2021 Type 1 dopamine receptor (D1R)-independent circadian food anticipatory activity in mice. PloS one 11 33556069
2020 Structure-Functional-Selectivity Relationship Studies of Novel Apomorphine Analogs to Develop D1R/D2R Biased Ligands. ACS medicinal chemistry letters 11 32184974
2018 A Functional Polymorphism in the DRD1 Gene, That Modulates Its Regulation by miR-504, Is Associated with Depressive Symptoms. Psychiatry investigation 11 29614853
2014 Aggression, DRD1 polymorphism, and lesion location in penetrating traumatic brain injury. CNS spectrums 11 24618367
2014 Association of dopamine receptor D1 (DRD1) polymorphisms with risperidone treatment response in Chinese schizophrenia patients. Neuroscience letters 11 25179995
2007 Haplotype association study between DRD1 gene and bipolar type I affective disorder in two samples from Canada and Sardinia. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 11 17066478
2023 Acupuncture modulates development of myopia by reducing NLRP3 inflammasome activation via the dopamine-D1R signaling pathway. Acupuncture in medicine : journal of the British Medical Acupuncture Society 10 37211683
2023 Cotransplantation of NSCs and ethyl stearate promotes synaptic plasticity in PD rats by Drd1/ERK/AP-1 signaling pathway. Journal of ethnopharmacology 10 37806537
2022 DRD1 and DRD4 are differentially expressed in breast tumors and breast cancer stem cells: pharmacological implications. Translational cancer research 10 36523297