Affinage

DRD1

D(1A) dopamine receptor · UniProt P21728

Length
446 aa
Mass
49.3 kDa
Annotated
2026-06-09
100 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DRD1 is a Gs-coupled dopamine receptor that converts dopaminergic input into intracellular signaling to regulate synaptic plasticity, motor learning, and peripheral physiology (PMID:33571432, PMID:20844125). Cryo-EM of DRD1-Gs complexes defines a polar orthosteric pocket for catecholamine recognition, an extended pocket that discriminates D1- from D2-like receptors, an inner-surface allosteric site that stabilizes bound dopamine, and the receptor-Gs interface governing coupling selectivity (PMID:33571432). Canonical Gs/cAMP output is routed to distinct effectors by context: in prefrontal cortex DRD1 acts upstream of a PKA/mTOR cascade driving synaptogenesis and LTP (PMID:28630404), in the nucleus accumbens it mediates cocaine-induced mTORC1 activation (PMID:26314207), and in lung endothelium it signals through cAMP/EPAC to inactivate HDAC6, preserving α-tubulin acetylation and barrier integrity (PMID:33456556). DRD1 also engages non-canonical and protein-interaction-dependent signaling: it associates with the tyrosine phosphatase Shp-2 to enable ERK1/2 activation (PMID:23328768), forms agonist-driven complexes with GluN1/NMDAR that potentiate calcium influx, ERK signaling, and striatal LTP (PMID:25070539), and partners with GHSR1a in hippocampal neurons to redirect signaling toward Gαq-PLC-IP3-Ca²⁺-CaMKII, driving synaptic reorganization (PMID:26590421). In the kidney, D1R/D5R heteromers couple cAMP and PLC to inhibit NHE3 and Na/K-ATPase and reduce sodium transport (PMID:24552847). At the cellular level DRD1 is required for hippocampal and striatal synaptic plasticity and learning (PMID:20844125, PMID:24843151), and cell-type-specific manipulations of striatal D1R neurons control motor skill acquisition and behavioral sensitization (PMID:31072930, PMID:22068054, PMID:21368124). Receptor abundance is set post-transcriptionally by miR-504 acting on the DRD1 3'UTR (PMID:19135651), and ligand-independent constitutive activity in neural stem cells restrains proliferation via PKC-CBP signaling (PMID:32052915).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2009 High

    Established that DRD1 expression is set post-transcriptionally, identifying a 3'UTR regulatory mechanism rather than purely transcriptional control of receptor levels.

    Evidence Luciferase reporter with site-directed mutagenesis plus miR-504 gain/loss-of-function

    PMID:19135651

    Open questions at the time
    • Does not address how receptor abundance translates to signaling output in vivo
    • Physiological consequence of the rs686 allelic difference not tested functionally
  2. 2010 High

    Showed that hippocampal D1R is causally required for associative learning and CA3-CA1 LTP, moving D1R from a striatal-centric view into hippocampal memory circuits.

    Evidence D1R knockout and intrahippocampal siRNA with in vivo LTP and multiple learning paradigms in mice

    PMID:20844125

    Open questions at the time
    • Downstream molecular effectors of hippocampal D1R not resolved here
    • Cell types within hippocampus mediating the effect not delineated
  3. 2011 High

    Dissected the cell-type-specific and topographic roles of striatal D1R neurons, distinguishing exploration from motor skill learning and establishing requirement for NMDAR within D1R neurons for sensitization.

    Evidence Region-specific D1R neuron ablation and conditional Grin1 deletion/rescue in D1R neurons with behavioral assays

    PMID:21368124 PMID:22068054

    Open questions at the time
    • Molecular basis of D1R-NMDAR interaction not addressed in these studies
    • How topographic differences arise mechanistically is unknown
  4. 2013 Medium

    Identified Shp-2 as a physical DRD1 partner required for ERK1/2 activation and linked persistent D1R/Shp-2/ERK signaling to L-DOPA-induced dyskinesia, and showed optogenetic D1R-MSN activity controls Tiam1 and cocaine sensitization.

    Evidence Reciprocal Co-IP and phospho-blotting in lesioned rat striatum; cell-type-specific optogenetics with molecular readouts

    PMID:23328768 PMID:23745104

    Open questions at the time
    • Structural basis of D1R/Shp-2 association unknown
    • Whether Shp-2 recruitment is direct or scaffold-mediated not established
  5. 2014 High

    Demonstrated DRD1 forms functional protein complexes — with GluN1/NMDAR in striatum and with D5R in kidney — that couple the receptor to dopamine-glutamate convergence and to combined cAMP/PLC sodium-transport control respectively.

    Evidence Co-IP, FRET, peptide disruption, region-specific KO, real-time biosensors, and transport assays

    PMID:24552847 PMID:24843151 PMID:25070539

    Open questions at the time
    • Stoichiometry and structural interface of these complexes unresolved
    • Whether the same complexes operate across other tissues not tested
  6. 2015 High

    Revealed signaling plasticity of DRD1: heteromerization with GHSR1a redirects output to Gαq-PLC-Ca²⁺-CaMKII, cocaine engages DRD1-dependent mTORC1, and peripheral D1R can act through cGMP/PKG to suppress tumor growth.

    Evidence Single-molecule imaging, FRET, Co-IP, genetic GHSR1a inactivation; D1R KO and conditional mTOR/Raptor deletion; xenograft models

    PMID:26314207 PMID:26477316 PMID:26590421

    Open questions at the time
    • Determinants selecting Gs versus Gq versus PKG output in a given cell unknown
    • cGMP/PKG coupling mechanism in cancer cells not mechanistically resolved
  7. 2018 Medium

    Placed D1R upstream of a PKA/mTOR cascade in prefrontal cortex driving synaptogenesis and LTP, extending the mTOR link beyond accumbens.

    Evidence Pharmacological epistasis with D1R, PKA, and mTOR inhibitors plus LTP recording in rat mPFC slices

    PMID:28630404

    Open questions at the time
    • Direct molecular link between PKA and mTOR activation not defined
    • Single-lab pharmacological epistasis without genetic confirmation
  8. 2020 High

    Uncovered ligand-independent constitutive DRD1 activity as a regulator of neural stem cell proliferation and differentiation through PKC-CBP signaling.

    Evidence Inverse agonists, siRNA, CRISPR A229T knock-in, and human cerebral organoid modeling

    PMID:32052915

    Open questions at the time
    • Mechanism generating constitutive activity in NSCs not structurally explained
    • Whether constitutive activity operates in mature neurons not tested
  9. 2021 High

    Provided the structural framework for DRD1 ligand recognition and G protein coupling, defining orthosteric, discriminating, and allosteric sites, and established a cAMP/EPAC/HDAC6/α-tubulin axis maintaining endothelial barrier function.

    Evidence Cryo-EM of five DRD1-Gs complexes with diverse ligands; D1R KO/knockdown with permeability assays and phospho-pathway dissection

    PMID:33456556 PMID:33571432

    Open questions at the time
    • Structures do not capture non-canonical Gq or heteromeric states
    • How allosteric modulation tunes downstream pathway choice not addressed
  10. 2023 High

    Linked DRD1 activity to neurotrophic signaling, showing D1R activation promotes TrkB surface translocation and BDNF responsiveness in direct-pathway striatal neurons, with dopamine depletion sequestering TrkB in SORCS-2-associated structures.

    Evidence FACS-enriched D1-SPN cultures, 6-OHDA rat model, and postmortem PD brain with TrkB translocation and SORCS-2 colocalization

    PMID:37252844

    Open questions at the time
    • Signaling steps connecting D1R activation to TrkB trafficking not fully resolved
    • Whether this axis is therapeutically reversible in vivo not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how DRD1 selects among its multiple coupling modes (Gs/cAMP, Gq/PLC, Shp-2/ERK, cGMP/PKG, constitutive PKC-CBP) within a single cell, and what structural states underlie its various heteromers.
  • No structure of DRD1 in a non-canonical or heteromeric signaling state
  • Cell-context rules governing effector choice unknown
  • Quantitative contribution of each pathway to physiology not partitioned

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 3
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 3
Partners
DRD2DRD5GHSR1AGRIN1NEFMPTPN11
Complex memberships
D1R/D5R heteromerD1R/GluN1 (NMDAR) complexDRD1-DRD2 heterodimerGHSR1a:DRD1:Gαq heteromer

Evidence

Reading pass · 21 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: (1) a polar interaction network essential for catecholamine-like agonist recognition at the orthosteric site; (2) specific motifs in an extended binding pocket that discriminate D1- from D2-like receptors; (3) an allosteric binding pocket at the inner receptor surface that stabilizes endogenous dopamine at the orthosteric site; and (4) key DRD1-Gs interface features determining G protein coupling selectivity. Cryo-electron microscopy (cryo-EM) of five DRD1-Gs complexes with three catechol-based agonists, one non-catechol agonist, and one positive allosteric modulator Cell High 33571432
2015 In hippocampal neurons, apo-GHSR1a (ghrelin receptor) dimerizes with DRD1 and forms preassembled GHSR1a:DRD1:Gαq heteromeric complexes. DRD1 agonism drives non-canonical Gαq-PLC-IP3-Ca2+ signaling at the expense of canonical Gαs-cAMP signaling, leading to CaMKII activation, glutamate receptor exocytosis, synaptic reorganization, and early markers of hippocampal synaptic plasticity. Genetic or pharmacological inactivation of GHSR1a blocks this DRD1-initiated pathway. Real-time single-molecule analysis, proximity measurements (FRET), co-immunoprecipitation, pharmacological and genetic GHSR1a inactivation, behavioral memory assays in mice Cell High 26590421
2014 Concomitant stimulation of D1R and NMDAR drives formation of endogenous D1R/GluN1 complexes in striatal medium spiny neurons. Preventing this complex with a cell-permeable TAT-GluN1C1 peptide leaves individual D1R and NMDAR signaling intact but abolishes D1R-mediated facilitation of NMDAR calcium influx and subsequent ERK activation, and reduces long-term potentiation in D1R-MSNs and behavioral sensitization to cocaine. Co-immunoprecipitation, cell-permeable peptide disruption (TAT-GluN1C1), electrophysiology in striatal slices, in vivo intra-striatal peptide delivery with behavioral assays Molecular psychiatry High 25070539
2013 In the striatum, D1R physically associates with the intracellular tyrosine phosphatase Shp-2, and this D1R/Shp-2 complex is required for D1R-mediated ERK1/2 activation. In hemiparkinsonian rats developing L-DOPA-induced dyskinesia, chronic D1R activation causes persistent Shp-2 phosphorylation and downstream ERK1/2 phosphorylation that outlasts L-DOPA washout, correlating with dyskinesia severity. Co-immunoprecipitation of endogenous D1R and Shp-2, western blotting for phospho-Shp-2 and phospho-ERK1/2 in 6-OHDA-lesioned rat striatum, pharmacological D1R agonist/antagonist treatments Neurobiology of disease Medium 23328768
2015 Cocaine-induced mTORC1 signaling in the nucleus accumbens is mediated specifically through DRD1. Cocaine increased phosphorylation of mTOR (Thr2446, Ser2481) and downstream targets 4E-BP1 and S6K; these increases were blocked by the D1R antagonist SCH23390 but not the D2R antagonist raclopride. D1R knockout mice showed reduced phospho-mTOR levels, and SKF81297 (D1R agonist) elevated them. Deletion of mTOR or its binding partner Raptor in D1R-expressing neurons reduced cocaine-induced locomotion. Pharmacological D1R/D2R antagonists, D1R knockout mice, dopamine-transporter knockout mice, D1R agonist treatment, conditional viral deletion of mTOR/Raptor in D1R neurons, western blotting Neuropharmacology High 26314207
2021 DRD1 signaling through the cAMP/EPAC pathway inactivates HDAC6, thereby preventing α-tubulin deacetylation and maintaining endothelial barrier function during mechanical stretch. Cyclic stretch activates GSK-3β, which phosphorylates and activates HDAC6, deacetylating α-tubulin; DRD1 activation counters this. DRD1 knockout or knockdown exacerbates mechanical stretch-induced lung endothelial hyperpermeability. DRD1 knockout mice, pulmonary DRD1 knockdown, isolated mouse lung vascular endothelial cells, pharmacological DRD1 agonists, western blotting for phospho-HDAC6 and acetyl-α-tubulin, permeability assays Theranostics High 33456556
2014 D1R and D5R co-localize in renal proximal tubule cells and physically interact (co-immunoprecipitation and FRET). D1R couples primarily to adenylyl cyclase/cAMP to inhibit NHE3 and NaKATPase and reduce sodium transport; the D1R/D5R heteromer additionally activates phospholipase C (PLC) to modulate sodium transport cooperatively. D5R siRNA or selective D5R antagonist blocks only the PLC pathway, whereas D1R siRNA blocks both cAMP and PLC pathways. Co-immunoprecipitation, FRET microscopy, D1R/D5R siRNA silencing, selective D5R antagonist (LE-PM436), real-time FRET biosensors for cAMP (ICUE3) and PLC (CYPHR), NHE3/NaKATPase activity assays Kidney international High 24552847
2009 miR-504 upregulates DRD1 expression by directly binding to the DRD1 3'UTR. The rs686 polymorphism in the 3'UTR creates differential miR-504 binding between alleles (A vs. G), causing allele-specific expression differences. Inhibition of miR-504 has the opposite (reducing) effect on DRD1 expression. Luciferase reporter assay, site-directed mutagenesis, miR-504 overexpression and inhibition, gene expression assay Biological psychiatry High 19135651
2020 DRD1 exhibits constitutive (ligand-independent) activity in human neural stem cells (NSCs). Inhibition of this constitutive activity by inverse agonists, or knock-in of the A229T reduced-activity mutant via CRISPR-Cas9, promotes NSC proliferation and impedes differentiation. The PKC-CBP pathway mediates these effects. These results were reproduced in human cerebral organoids, where reducing DRD1 constitutive activity induced organoid expansion and folding. Inverse agonist pharmacology, DRD1 siRNA knockdown, CRISPR-Cas9 knock-in of A229T mutant, human cerebral organoid modeling, PKC-CBP pathway inhibitor studies Stem cells (Dayton, Ohio) High 32052915
2023 DRD1 activation causes enhanced TrkB translocation to the cell surface and increased BDNF sensitivity in direct pathway striatal neurons (dSPNs). Dopamine depletion (in cultured dSPNs, 6-OHDA-treated 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, protecting them from lysosomal degradation. FACS-enriched D1-expressing SPN cultures, 6-OHDA rat model, postmortem PD brain immunostaining, TrkB surface translocation assays, DRD1 agonist/antagonist treatments, co-localization with SORCS-2 Cell reports High 37252844
2017 NEFM (neurofilament medium polypeptide) co-immunoprecipitates with DRD1 in adrenocortical cells. NEFM silencing amplifies DRD1 agonist (fenoldopam)-stimulated aldosterone secretion and potentiates DRD1 antagonist (SCH23390)-mediated inhibition. NEFM expression is stimulated by fenoldopam, and immunohistochemistry shows DRD1 is primarily intracellular (internalized) in NEFM-expressing zona glomerulosa-like cells, suggesting NEFM acts as a negative regulator of aldosterone production partly by facilitating DRD1 internalization. Co-immunoprecipitation, siRNA silencing of NEFM in H295R cells, aldosterone secretion assays with D1R agonist/antagonist, immunohistochemistry for DRD1 localization Hypertension (Dallas, Tex. : 1979) Medium 28584012
2022 DRD1 and DRD2 can form heterodimers. Using fluorescent protein-based multicolor biosensors monitoring individual receptor activation states in live cells, DRD1-DRD2 heterodimers show differential receptor crosstalk dependent on dopamine concentration: DRD1 activation is selectively inhibited at micromolar (phasic) dopamine levels, while DRD2 is inhibited only at nanomolar (tonic) dopamine concentrations within the heterodimer. Live-cell fluorescent protein-based multicolor biosensors for individual DRD1 and DRD2 activation states, dose-response experiments at nanomolar to micromolar dopamine concentrations Progress in neurobiology Medium 35364139
2018 D1R activation in the medial prefrontal cortex (mPFC) by l-SPD (levo-stepholidine) activates a D1R/PKA/mTOR signaling cascade, increasing synaptogenesis-related proteins (PSD-95, synapsin I) and inducing long-term synaptic potentiation (LTP) in the mPFC. D1R antagonist, PKA inhibitor, or mTOR inhibitor each blocked these effects, placing D1R upstream of PKA and mTOR in this signaling pathway. Pharmacological D1R agonist/antagonist, PKA inhibitor, mTOR inhibitor in rat CMS depression model; western blotting for downstream targets; LTP electrophysiology in mPFC slices Scientific reports Medium 28630404
2015 D1R signaling in breast cancer cells operates through the cGMP/protein kinase G (PKG) pathway. D1R agonists suppressed cell viability, inhibited invasion, and induced apoptosis in multiple breast cancer cell lines via this pathway. The peripheral D1R agonist fenoldopam dramatically suppressed tumor growth in two mouse xenograft models with D1R-expressing tumors. In vitro cell viability, invasion and apoptosis assays with D1R agonists; cGMP/PKG pathway pharmacology; in vivo mouse xenograft models with fenoldopam treatment Oncogene Medium 26477316
2010 D1R (Drd1a) is required for hippocampal associative learning and CA3-CA1 synaptic plasticity (LTP). D1R knockout mice (Drd1a-/-) and mice with intrahippocampal Drd1a-siRNA showed markedly reduced spatial learning, fear learning, classical trace eyeblink conditioning, in vivo LTP at the CA3-CA1 synapse, and LTP-induced Egr1 expression. The siRNA and knockout phenotypes were indistinguishable, confirming the effect is specifically due to hippocampal D1R loss. D1R knockout mice, intrahippocampal siRNA injection, in vivo LTP recording at CA3-CA1 synapse, multiple behavioral learning paradigms, Egr1 immunohistochemistry The Journal of neuroscience High 20844125
2014 DG (dentate gyrus)-specific D1R knockout impairs contextual fear memory and causes generalized fear between similar contexts, while DG D5R knockout does not. In DG D1R KO mice, c-Fos expression in DG is basally elevated and fails to increase upon novel context exposure, indicating D1R is required for formation of distinct contextual representations. Spatially restricted conditional KO mice for D1R or D5R in dentate gyrus granule cells, contextual fear conditioning, c-Fos immunohistochemistry Proceedings of the National Academy of Sciences of the United States of America High 24843151
2012 Molecular modeling and dynamics simulations identified that hydrogen bonding of the hydroxyl group on the D ring of l-SPD (stepholidine) with N6.55, combined with hydrophobic stacking between I3.40, F6.44 and W6.48, mediates the agonist effect on D1R. The absence of this hydrophobic stacking in D2R and D3R explains why l-SPD acts as an antagonist there rather than an agonist. Homology modeling of D1R, D2R, D3R; automated molecular docking; molecular dynamics simulations The journal of physical chemistry. B Low 22702398
2019 Stable D1R neuronal ensembles emerge in the dorsolateral striatum during motor learning and fire sequentially during learned behavior. Selective chemogenetic silencing of D1R neurons (but not D2R neurons) impaired initiation of the learned motor action, while D2R neuron silencing impaired suppression of erroneous movements during intertrial intervals. Long-term two-photon calcium imaging in D1R-Cre and D2R-Cre transgenic mice during cued lever-pushing task learning, chemogenetic (DREADD) cell-type-specific silencing Proceedings of the National Academy of Sciences of the United States of America High 31072930
2011 D1R-expressing striatonigral neurons in the associative (dorsomedial) striatum stimulate locomotion/exploration and are required for gradual motor skill acquisition in the sensorimotor (dorsolateral) striatum. Selective ablation of D1R-expressing neurons in specific striatal subregions revealed dissociable topographic roles: DMS D1R neurons regulate exploration, DLS D1R neurons mediate motor skill learning. Cell-type- and region-specific ablation of D1R or D2R striatal neurons using Cre-dependent toxin receptor strategy; locomotor, novelty, motor learning, and pharmacological behavioral assays The EMBO journal High 22068054
2011 NMDAR signaling specifically in D1R-expressing MSNs in the nucleus accumbens is required for amphetamine behavioral sensitization. Conditional deletion of NR1 (Grin1) selectively from D1R neurons attenuated sensitization; virus-mediated restoration of NR1 in D1R neurons of NAc rescued sensitization. Importantly, balanced loss of NMDARs from both D1R and D2R MSNs is permissive for sensitization, while unbalanced loss from D1R neurons alone prevents it. Conditional knockout of Grin1 in D1R or D2R neurons, viral NR1 restoration in NAc D1R neurons, viral NR1 inactivation in remaining NAc neurons, amphetamine sensitization behavioral assay Proceedings of the National Academy of Sciences of the United States of America High 21368124
2013 Optogenetic activation of D1R-MSNs (but not D2R-MSNs) in NAc causes down-regulation of Tiam1 (actin cytoskeleton regulator), mimicking the effect of cocaine self-administration. Optogenetic inhibition of D1R-MSNs during cocaine exposure reversed cocaine-induced locomotor sensitization and blocked the cocaine-mediated decrease in Tiam1 gene expression and protein. Optogenetics (ChR2 activation, eNpHR3.0 inhibition) of NAc D1R- or D2R-MSNs, cocaine self-administration, qPCR and western blot for Tiam1 Frontiers in molecular neuroscience Medium 23745104

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 190 30644390
2011 Differential regulation of motor control and response to dopaminergic drugs by D1R and D2R neurons in distinct dorsal striatum subregions. The EMBO journal 159 22068054
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
2021 Ligand recognition and allosteric regulation of DRD1-Gs signaling complexes. Cell 133 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 107 28065827
2015 Hippocampal Dopamine/DRD1 Signaling Dependent on the Ghrelin Receptor. Cell 101 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 96 19135651
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 92 23908605
2013 Contrasting changes in DRD1 and DRD2 splice variant expression in schizophrenia and affective disorders, and associations with SNPs in postmortem brain. Molecular psychiatry 92 24322206
2007 Significant association of DRD1 with nicotine dependence. Human genetics 90 18092181
2006 Immunohistochemical localization of dopamine receptor subtypes (D1R-D5R) in Alzheimer's disease brain. Brain research 90 17182012
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 79 30655356
2018 Exercise Reduces Dopamine D1R and Increases D2R in Rats: Implications for Addiction. Medicine and science in sports and exercise 77 29613999
2015 Expression and therapeutic targeting of dopamine receptor-1 (D1R) in breast cancer. Oncogene 72 26477316
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
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 71 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 68 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 55 28316027
2010 Systematic analysis of dopamine receptor genes (DRD1-DRD5) in antipsychotic-induced weight gain. The pharmacogenomics journal 51 20714340
2008 Blood pressure and renal sodium handling in relation to genetic variation in the DRD1 promoter and GRK4. Hypertension (Dallas, Tex. : 1979) 50 18413491
2014 Cannabinoid, melanocortin and opioid receptor expression on DRD1 and DRD2 subpopulations in rat striatum. Frontiers in neuroanatomy 49 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 36 23328768
2013 The expression of MC4Rs in D1R neurons regulates food intake and locomotor sensitization to cocaine. Genes, brain, and behavior 34 23786641
2002 Linkage disequilibrium between dopamine D1 receptor gene (DRD1) and bipolar disorder. Biological psychiatry 34 12488059
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 29 31862611
2015 Essential role of D1R in the regulation of mTOR complex1 signaling induced by cocaine. Neuropharmacology 28 26314207
2012 DRD1 rs4532 polymorphism: a potential pharmacogenomic marker for treatment response to antipsychotic drugs. Schizophrenia research 28 23036699
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
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 27 34658761
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 27 29089442
2014 The cooperative roles of the dopamine receptors, D1R and D5R, on the regulation of renal sodium transport. Kidney international 27 24552847
2014 Dopamine receptor gene (DRD1-DRD5) expression changes as stress factors associated with breast cancer. Asian Pacific journal of cancer prevention : APJCP 27 25556472
2007 Association of the dopamine receptor D1 gene, DRD1, with inattention symptoms in families selected for reading problems. Molecular psychiatry 27 17310237
2020 Constitutive activity of a G protein-coupled receptor, DRD1, contributes to human cerebral organoid formation. Stem cells (Dayton, Ohio) 26 32052915
2017 Activation of D1R/PKA/mTOR signaling cascade in medial prefrontal cortex underlying the antidepressant effects of l-SPD. Scientific reports 26 28630404
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 Dopamine D1R-neuron cacna1c deficiency: a new model of extinction therapy-resistant post-traumatic stress. Molecular psychiatry 24 32332995
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
2022 Dopamine D1R Receptor Stimulation as a Mechanistic Pro-cognitive Target for Schizophrenia. Schizophrenia bulletin 23 34423843
2004 Ethnic origin determines the impact of genetic variants in dopamine receptor gene (DRD1) concerning essential hypertension. American journal of hypertension 23 15607627
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
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 21 31920618
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
2021 D1R- and D2R-Medium-Sized Spiny Neurons Diversity: Insights Into Striatal Vulnerability to Huntington's Disease Mutation. Frontiers in cellular neuroscience 20 33642998
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
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 18 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 15 39129007
2023 Selective Activation of NAc D1R-VP/LH Circuits Promotes Reanimation From Sevoflurane Anesthesia in Mice. Anesthesia and analgesia 15 36944111
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) 14 34495077
2019 β-arrestin2 alleviates L-dopa-induced dyskinesia via lower D1R activity in Parkinson's rats. Aging 14 31891566
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
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 13 37094933
2022 Visualization of differential GPCR crosstalk in DRD1-DRD2 heterodimer upon different dopamine levels. Progress in neurobiology 13 35364139
2022 Per2 Expression Regulates the Spatial Working Memory of Mice through DRD1-PKA-CREB Signaling. Molecular neurobiology 13 35508866
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
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 12 38246990
2021 Type 1 dopamine receptor (D1R)-independent circadian food anticipatory activity in mice. PloS one 12 33556069
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
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
2024 Dopamine promotes osteogenic differentiation of PDLSCs by activating DRD1 and DRD2 during orthodontic tooth movement via ERK1/2 signaling pathway. Regenerative therapy 10 38617443
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
2021 Modafinil rescues repeated morphine-induced synaptic and behavioural impairments via activation of D1R-ERK-CREB pathway in medial prefrontal cortex. Addiction biology 10 34647651

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