Gene Symbol: Oprd1
Description: opioid receptor, delta 1
Alias: DOR, DOR-1, Nbor, mDOR, delta-type opioid receptor, D-OR-1, K56, MSL-2, delta 1 opioid receptor
Species: mouse
Products:     Oprd1

Top Publications

  1. Erbs E, Faget L, Scherrer G, Kessler P, Hentsch D, Vonesch J, et al. Distribution of delta opioid receptor-expressing neurons in the mouse hippocampus. Neuroscience. 2012;221:203-13 pubmed publisher
    ..Indeed, they are mostly expressed in parvalbumin-immunopositive neurons both in the Ammon's horn and dentate gyrus. These receptors, therefore, most likely participate in the dynamic regulation of hippocampal activity. ..
  2. Gupta A, Mulder J, Gomes I, Rozenfeld R, Bushlin I, Ong E, et al. Increased abundance of opioid receptor heteromers after chronic morphine administration. Sci Signal. 2010;3:ra54 pubmed publisher
    ..Because of its distinct signaling properties, the mu-delta heteromer could be a therapeutic target in the treatment of chronic pain and addiction. ..
  3. Wang H, Zhao B, Zhong Y, Li K, Li Z, Wang Q, et al. Coexpression of delta- and mu-opioid receptors in nociceptive sensory neurons. Proc Natl Acad Sci U S A. 2010;107:13117-22 pubmed publisher
    ..Importantly, both DOR and MOR agonists reduce depolarization-induced Ca(2+) currents in single small DRG neurons and inhibit afferent C-..
  4. Bigliardi Qi M, Gaveriaux Ruff C, Zhou H, Hell C, Bady P, Rufli T, et al. Deletion of delta-opioid receptor in mice alters skin differentiation and delays wound healing. Differentiation. 2006;74:174-85 pubmed
    ..Several findings suggest that the delta-opioid receptor (DOR) and its endogenous ligands (enkephalins) are important players in cell differentiation and proliferation...
  5. Ghozland S, Matthes H, Simonin F, Filliol D, Kieffer B, Maldonado R. Motivational effects of cannabinoids are mediated by mu-opioid and kappa-opioid receptors. J Neurosci. 2002;22:1146-54 pubmed
    ..Thus, an opposing activity of mu- and kappa-opioid receptors in modulating reward pathways forms the basis for the dual euphoric-dysphoric activity of THC. ..
  6. Nishi M, Houtani T, Noda Y, Mamiya T, Sato K, Doi T, et al. Unrestrained nociceptive response and disregulation of hearing ability in mice lacking the nociceptin/orphaninFQ receptor. EMBO J. 1997;16:1858-64 pubmed
    ..On the other hand, we found insufficient recovery of hearing ability from the adaptation to sound exposure in the mutant mice. Thus, the nociceptin system appears to participate in the regulation of the auditory system. ..
  7. Evans C, Keith D, Morrison H, Magendzo K, Edwards R. Cloning of a delta opioid receptor by functional expression. Science. 1992;258:1952-5 pubmed
    ..The sequence shows homology to G protein-coupled receptors, in particular the receptors for somatostatin, angiotensin, and interleukin-8. ..
  8. Rezai X, Faget L, Bednarek E, Schwab Y, Kieffer B, Massotte D. Mouse ? opioid receptors are located on presynaptic afferents to hippocampal pyramidal cells. Cell Mol Neurobiol. 2012;32:509-16 pubmed publisher
    ..In the mouse hippocampus, expression of functional delta opioid receptors is therefore mostly associated with interneurons emphasizing a presynaptic modulatory effect on the pyramidal cell firing rate. ..
  9. Xu C, Hong M, Zhang L, Hou Y, Wang Y, Wang F, et al. Serine 363 of the {delta}-opioid receptor is crucial for adopting distinct pathways to activate ERK1/2 in response to stimulation with different ligands. J Cell Sci. 2010;123:4259-70 pubmed publisher
    ..However, such functional differences of ERK disappeared with the mutation of Ser363. Therefore, the present study reveals a crucial role for Ser363 in agonist-specific regulation of ERK activation patterns and functions. ..

More Information


  1. Scherrer G, Imamachi N, Cao Y, Contet C, Mennicken F, O donnell D, et al. Dissociation of the opioid receptor mechanisms that control mechanical and heat pain. Cell. 2009;137:1148-59 pubmed publisher
    ..Using a DOReGFP reporter mouse we now show that the DOR and MOR are, in fact, expressed by different subsets of primary afferents...
  2. Nadal X, Baños J, Kieffer B, Maldonado R. Neuropathic pain is enhanced in delta-opioid receptor knockout mice. Eur J Neurosci. 2006;23:830-4 pubmed
    We have evaluated the possible involvement of delta-opioid receptor (DOR) in the development and expression of neuropathic pain...
  3. Law P, Erickson Herbrandson L, Zha Q, Solberg J, Chu J, Sarre A, et al. Heterodimerization of mu- and delta-opioid receptors occurs at the cell surface only and requires receptor-G protein interactions. J Biol Chem. 2005;280:11152-64 pubmed
    ..expressed mu-opioid receptor (MOR) and the ponasterone A-induced expression of delta-opioid receptor (DOR) in EcR293 cells...
  4. Zhu Y, King M, Schuller A, Nitsche J, Reidl M, Elde R, et al. Retention of supraspinal delta-like analgesia and loss of morphine tolerance in delta opioid receptor knockout mice. Neuron. 1999;24:243-52 pubmed
    Gene targeting was used to delete exon 2 of mouse DOR-1, which encodes the delta opioid receptor...
  5. Knapp R, Malatynska E, Collins N, Fang L, Wang J, Hruby V, et al. Molecular biology and pharmacology of cloned opioid receptors. FASEB J. 1995;9:516-25 pubmed
    ..A molecular model of the human delta opioid receptor is included in this review. ..
  6. Martin M, Matifas A, Maldonado R, Kieffer B. Acute antinociceptive responses in single and combinatorial opioid receptor knockout mice: distinct mu, delta and kappa tones. Eur J Neurosci. 2003;17:701-8 pubmed
    We have examined responses of mice lacking mu, delta and kappa opioid receptor (MOR, DOR and KOR, respectively) genes, as well as combinatorial mutants, in several pain models...
  7. Raynor K, Kong H, Chen Y, Yasuda K, Yu L, Bell G, et al. Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors. Mol Pharmacol. 1994;45:330-4 pubmed
    ..The availability of the cloned receptors will facilitate the identification and development of more specific and selective compounds with greater therapeutic potential and fewer undesirable side effects. ..
  8. Kieffer B, Evans C. Opioid receptors: from binding sites to visible molecules in vivo. Neuropharmacology. 2009;56 Suppl 1:205-12 pubmed publisher
    ..Importantly, we will identify a number of research directions that are likely to develop during the next decade. ..
  9. Le Merrer J, Plaza Zabala A, Del Boca C, Matifas A, Maldonado R, Kieffer B. Deletion of the ? opioid receptor gene impairs place conditioning but preserves morphine reinforcement. Biol Psychiatry. 2011;69:700-3 pubmed publisher
    ..Collectively, the data suggest that ? receptor activity is not involved in morphine reinforcement but facilitates place conditioning. This study reveals a novel aspect of ? opioid receptor function in addiction-related behaviors. ..
  10. Chefer V, Kieffer B, Shippenberg T. Basal and morphine-evoked dopaminergic neurotransmission in the nucleus accumbens of MOR- and DOR-knockout mice. Eur J Neurosci. 2003;18:1915-22 pubmed
    ..in the nucleus accumbens (NAc) of wild-type mice and those with a constitutive deletion of mu (MOR)- or delta (DOR)-opioid receptors. Locomotor activity was assessed in these same animals...
  11. Goody R, Oakley S, Filliol D, Kieffer B, Kitchen I. Quantitative autoradiographic mapping of opioid receptors in the brain of delta-opioid receptor gene knockout mice. Brain Res. 2002;945:9-19 pubmed
    Using quantitative receptor autoradiography we have determined if deletion of the delta-opioid receptor gene (Oprd1) results in compensatory changes in the expression of other opioid receptors...
  12. Filliol D, Ghozland S, Chluba J, Martin M, Matthes H, Simonin F, et al. Mice deficient for delta- and mu-opioid receptors exhibit opposing alterations of emotional responses. Nat Genet. 2000;25:195-200 pubmed
    ..The mu-, delta- and kappa- opioid receptors (encoded by Oprm, Oprd1 and Oprk1, respectively) mediate the biological activity of opioids...
  13. Slowe S, Simonin F, Kieffer B, Kitchen I. Quantitative autoradiography of mu-,delta- and kappa1 opioid receptors in kappa-opioid receptor knockout mice. Brain Res. 1999;818:335-45 pubmed
    ..This effect was most notable in the nucleus accumbens and the vertical limb of the diagonal band, and suggests there may be functional interactions between mu- and delta-receptors and kappa1- and delta-receptors in mouse brain. ..
  14. Jordan B, Devi L. G-protein-coupled receptor heterodimerization modulates receptor function. Nature. 1999;399:697-700 pubmed
    ..Furthermore, the kappa-delta heterodimer synergistically binds highly selective agonists and potentiates signal transduction. Thus, heterodimerization of these GPCRs represents a novel mechanism that modulates their function. ..
  15. Gaveriaux Ruff C, Nozaki C, Nadal X, Hever X, Weibel R, Matifas A, et al. Genetic ablation of delta opioid receptors in nociceptive sensory neurons increases chronic pain and abolishes opioid analgesia. Pain. 2011;152:1238-48 pubmed publisher
    ..The conditional knockout of delta-opioid receptor in primary afferent Na(V)1.8 neurons augmented mechanical allodynia in persistent pain models and abolished delta opioid analgesia in these models. ..
  16. van Rijn R, Whistler J. The delta(1) opioid receptor is a heterodimer that opposes the actions of the delta(2) receptor on alcohol intake. Biol Psychiatry. 2009;66:777-84 pubmed publisher
  17. Scherrer G, Tryoen Toth P, Filliol D, Matifas A, Laustriat D, Cao Y, et al. Knockin mice expressing fluorescent delta-opioid receptors uncover G protein-coupled receptor dynamics in vivo. Proc Natl Acad Sci U S A. 2006;103:9691-6 pubmed
    ..We created mice where the delta-opioid receptor (DOR) is replaced by an active DOR-EGFP fusion...
  18. Gaveriaux Ruff C, Simonin F, Filliol D, Kieffer B. Enhanced humoral response in kappa-opioid receptor knockout mice. J Neuroimmunol. 2003;134:72-81 pubmed
    ..These results show that endogenous activation of kappa-opioid receptors may exert a tonic inhibition of antibody (Ab) response. ..
  19. Gutierrez Cuesta J, Burokas A, Mancino S, Kummer S, Martín García E, Maldonado R. Effects of genetic deletion of endogenous opioid system components on the reinstatement of cocaine-seeking behavior in mice. Neuropsychopharmacology. 2014;39:2974-88 pubmed publisher
    ..have used genetically modified mice to evaluate the involvement of ?-opioid receptor (MOR) and ?-opioid receptor (DOR) and their main endogenous ligands, the enkephalins derived from proenkephalin (PENK) and prodynorphin (PDYN), in ..
  20. García Sevilla J, Ferrer Alcon M, Martin M, Kieffer B, Maldonado R. Neurofilament proteins and cAMP pathway in brains of mu-, delta- or kappa-opioid receptor gene knock-out mice: effects of chronic morphine administration. Neuropharmacology. 2004;46:519-30 pubmed
    ..The induction of heterologous receptor adaptations in mu-KO mice may explain this paradoxical effect of morphine. ..
  21. Treuner M, Kozak C, Gallahan D, Grosse R, Muller T. Cloning and characterization of the mouse gene encoding mammary-derived growth inhibitor/heart-fatty acid-binding protein. Gene. 1994;147:237-42 pubmed
  22. Somvanshi R, Kumar U. ?-opioid receptor and somatostatin receptor-4 heterodimerization: possible implications in modulation of pain associated signaling. PLoS ONE. 2014;9:e85193 pubmed publisher
  23. Laurent V, Leung B, Maidment N, Balleine B. ?- and ?-opioid-related processes in the accumbens core and shell differentially mediate the influence of reward-guided and stimulus-guided decisions on choice. J Neurosci. 2012;32:1875-83 pubmed publisher
    ..Here, we evaluated the role of ?-opioid receptor (MOR) and ?-opioid receptor (DOR) in the nucleus accumbens in the way these motivational processes influence choice using outcome revaluation and ..
  24. Jones J, Luba R, Vogelman J, Comer S. Searching for evidence of genetic mediation of opioid withdrawal by opioid receptor gene polymorphisms. Am J Addict. 2016;25:41-8 pubmed publisher
    ..COWS) from this procedure was correlated with genotype information for variants of OPRM1 (rs1799971; rs6848893), OPRD1 (rs10753331; rs2234918; rs581111; rs678849; rs1042114), and OPRK1 (rs6473797; rs963549)...
  25. BANGHART M, Neufeld S, Wong N, Sabatini B. Enkephalin Disinhibits Mu Opioid Receptor-Rich Striatal Patches via Delta Opioid Receptors. Neuron. 2015;88:1227-1239 pubmed publisher
    ..These results suggest that enkephalin gates limbic information flow in dorsal striatum, acting via a patch-specific function for delta opioid receptors. ..
  26. Befort K, Mattei M, Roeckel N, Kieffer B. Chromosomal localization of the delta opioid receptor gene to human 1p34.3-p36.1 and mouse 4D bands by in situ hybridization. Genomics. 1994;20:143-5 pubmed
  27. Nitsche J, Schuller A, King M, Zengh M, Pasternak G, Pintar J. Genetic dissociation of opiate tolerance and physical dependence in delta-opioid receptor-1 and preproenkephalin knock-out mice. J Neurosci. 2002;22:10906-13 pubmed
    Previous experiments have shown that mice lacking a functional delta-opioid receptor (DOR-1) gene do not develop analgesic tolerance to morphine...
  28. Mogil J, Richards S, O Toole L, Helms M, Mitchell S, Belknap J. Genetic sensitivity to hot-plate nociception in DBA/2J and C57BL/6J inbred mouse strains: possible sex-specific mediation by delta2-opioid receptors. Pain. 1997;70:267-77 pubmed
    ..An obvious candidate gene located in this same chromosomal region is Oprd1, which encodes the murine delta-opioid receptor...
  29. Clarke S, Czyzyk T, Ansonoff M, Nitsche J, Hsu M, Nilsson L, et al. Autoradiography of opioid and ORL1 ligands in opioid receptor triple knockout mice. Eur J Neurosci. 2002;16:1705-12 pubmed
    ..Labelling of the ORL1 receptor with [3H]nociceptin showed region-dependent quantitative increases in triple knockout brains indicating a close relationship between the two systems in specific brain areas. ..
  30. Scherrer G, Befort K, Contet C, Becker J, Matifas A, Kieffer B. The delta agonists DPDPE and deltorphin II recruit predominantly mu receptors to produce thermal analgesia: a parallel study of mu, delta and combinatorial opioid receptor knockout mice. Eur J Neurosci. 2004;19:2239-48 pubmed
  31. Contet C, Matifas A, Kieffer B. No evidence for G-protein-coupled epsilon receptor in the brain of triple opioid receptor knockout mouse. Eur J Pharmacol. 2004;492:131-6 pubmed
    ..We conclude that the brain epsilon site involves mu, delta and/or kappa receptors, possibly coupled to nonclassical G proteins. ..
  32. Sedqi M, Roy S, Ramakrishnan S, Loh H. Expression cloning of a full-length cDNA encoding delta opioid receptor from mouse thymocytes. J Neuroimmunol. 1996;65:167-70 pubmed
    ..The studies represent the first report of a full-length opioid receptor in the immune system. ..
  33. Herron B, Liddell R, Parker A, Grant S, Kinne J, Fisher J, et al. A mutation in stratifin is responsible for the repeated epilation (Er) phenotype in mice. Nat Genet. 2005;37:1210-2 pubmed
    ..Er/+ mice expressed a truncated Sfn protein, which probably contributes to the defects in Er/Er and Er/+ epidermis and to cancer development in Er/+ mice. ..
  34. Georganta E, Agalou A, Georgoussi Z. Multi-component signaling complexes of the delta-opioid receptor with STAT5B and G proteins. Neuropharmacology. 2010;59:139-48 pubmed publisher
    ..We can thus conclude that STAT5B signaling can be modulated by its coupling with a specific subset of G protein subunits, revealing a novel signaling mechanism for the transcriptional regulation of STAT5B-dependent genes. ..
  35. Gaveriaux Ruff C, Filliol D, Simonin F, Matthes H, Kieffer B. Immunosuppression by delta-opioid antagonist naltrindole: delta- and triple mu/delta/kappa-opioid receptor knockout mice reveal a nonopioid activity. J Pharmacol Exp Ther. 2001;298:1193-8 pubmed
    ..Therefore, the postulated inhibitory activity of naltrindole in the graft rejection process is mediated by a target, which remains to be discovered. ..
  36. Kest B, Jenab S, Brodsky M, Elliott K, Inturrisi C. Supraspinal delta opioid receptor mRNA levels are not altered in [D-Ala2]deltorphin II tolerant mice. J Neurosci Res. 1994;39:674-9 pubmed
    Delta opioid receptor (DOR) mRNA levels were studied in mice rendered tolerant to [D-Ala2]deltorphin II by 4 days of repeated intracerebroventricular administration (10 micrograms, [tid])...
  37. Dubois D, Gendron L. Delta opioid receptor-mediated analgesia is not altered in preprotachykinin A knockout mice. Eur J Neurosci. 2010;32:1921-9 pubmed publisher
    ..Consequently, our results suggest that SP is not essential for membrane insertion and for the functional emergence of DOPR. ..
  38. Walwyn W, Maidment N, Sanders M, Evans C, Kieffer B, Hales T. Induction of delta opioid receptor function by up-regulation of membrane receptors in mouse primary afferent neurons. Mol Pharmacol. 2005;68:1688-98 pubmed
    ..However, up-regulation of cell-surface delta receptors induces their coupling to Ca2+ channels. Pharmacological approaches that increase functional delta receptor expression may reveal a novel target for analgesic therapy. ..
  39. Tang X, Chen Y, Ran H, Jiang Y, He B, Wang B, et al. Systemic morphine treatment derails normal uterine receptivity, leading to embryo implantation failure in mice. Biol Reprod. 2015;92:118 pubmed publisher
    ..These novel findings add a new line of evidence to better understand the causes for obvious adverse effects of opioid abuse on pregnancy success in women. ..
  40. Rozenfeld R, Bushlin I, Gomes I, Tzavaras N, Gupta A, Neves S, et al. Receptor heteromerization expands the repertoire of cannabinoid signaling in rodent neurons. PLoS ONE. 2012;7:e29239 pubmed publisher
    ..expanded signaling responses by a single ligand and focused on interactions between CB?R and delta opioid receptor (DOR)...
  41. Bigliardi P, Neumann C, Teo Y, Pant A, Bigliardi Qi M. Activation of the ?-opioid receptor promotes cutaneous wound healing by affecting keratinocyte intercellular adhesion and migration. Br J Pharmacol. 2015;172:501-14 pubmed publisher
    ..This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2. ..
  42. Fu C, Xia R, Zhang T, Lu Y, Zhang S, Yu Z, et al. Hemokinin-1(4-11)-induced analgesia selectively up-regulates ?-opioid receptor expression in mice. PLoS ONE. 2014;9:e90446 pubmed publisher
    ..In contrast, both mRNA and protein levels of DOR have been up-regulated significantly, indicating that the enhanced expression of ? opioid receptor negatively ..
  43. Boutin H, Catherine A, Mackenzie E, Jauzac P, Dauphin F. Long-term alterations in mu, delta and kappa opioidergic receptors following middle cerebral artery occlusion in mice. Acta Neuropathol. 2007;114:491-500 pubmed
    ..Changes in opioidergic receptor expression in these regions may be involved in the long-term consequences of stroke and could be used as biomarker of neuronal alteration through the use of imaging techniques in the clinic. ..
  44. Pol O, Valle L, Puig M. Antisense oligodeoxynucleotides to mu- and delta-opioid receptor mRNA block the enhanced effects of opioids during intestinal inflammation. Eur J Pharmacol. 2001;428:127-36 pubmed
  45. Chen Y, Kong S, Tang X, Fu Y, Wang B, Zhang S, et al. Preimplantation mouse embryo is a target for opioid ligand-receptor signaling. Biol Reprod. 2014;91:4 pubmed publisher
  46. Schmidt Y, Gaveriaux Ruff C, Machelska H. ?-Opioid receptor antibody reveals tissue-dependent specific staining and increased neuronal ?-receptor immunoreactivity at the injured nerve trunk in mice. PLoS ONE. 2013;8:e79099 pubmed publisher
    ..Furthermore, our findings suggest a rigorous tissue-dependent characterization of antibodies' specificity, preferably using knockout animals. ..
  47. Kieffer B, Befort K, Gaveriaux Ruff C, Hirth C. The delta-opioid receptor: isolation of a cDNA by expression cloning and pharmacological characterization. Proc Natl Acad Sci U S A. 1992;89:12048-52 pubmed
    ..4 nM), stereospecific binding sites for the - enantiomers of levorphanol and naloxone, and the selectivity profile of a delta receptor, as determined by competition experiments with a set of mu-, delta-, and kappa-opioid ligands. ..
  48. Danciger M, Brady J, Adamson M, Farber D, Piatigorsky J, Kozak C. Chromosomal localization of the genes for five zinc finger proteins expressed in mouse lens. Genomics. 1995;28:39-43 pubmed
    ..Because the zinc finger proteins encoded by these genes may be involved in regulating other genes that are expressed in lens, they can be considered candidates for the large number of yet unmapped cataract loci. ..
  49. Keith D, Anton B, Evans C. Characterization and mapping of a delta opioid receptor clone from NG108-15 cells. Proc West Pharmacol Soc. 1993;36:299-306 pubmed
  50. Archer Lahlou E, Audet N, Amraei M, Huard K, Paquin Gobeil M, Pineyro G. Src promotes delta opioid receptor (DOR) desensitization by interfering with receptor recycling. J Cell Mol Med. 2009;13:147-63 pubmed publisher
    ..In the case of delta opioid receptors (DOR), desensitization is especially swift because receptors are rapidly internalized and are poorly recycled to the ..
  51. McCarthy L, Nitsche J, Pintar J, Rogers T. The delta-opioid receptor participates in T-cell development by promoting negative selection. J Neuroimmunol. 2004;153:91-8 pubmed
    The delta-opioid receptor-1 (DOR-1) as well as delta-opioid enkephalin peptides are expressed during maturation of T cells, although the functional significance of their expression remains unclear...
  52. Börner C, Wöltje M, Hollt V, Kraus J. STAT6 transcription factor binding sites with mismatches within the canonical 5'-TTC...GAA-3' motif involved in regulation of delta- and mu-opioid receptors. J Neurochem. 2004;91:1493-500 pubmed
    ..In contrast, the non-canonical STAT6 site of the delta-opioid receptor binds STAT6 with similar high activity as a perfectly palindromic STAT6 site and is strongly inducible by IL-4. ..
  53. Zhu X, Wang C, Cheng Z, Wu Y, Zhou D, Pei G. The carboxyl terminus of mouse delta-opioid receptor is not required for agonist-dependent activation. Biochem Biophys Res Commun. 1997;232:513-6 pubmed
    ..Their membrane localization and ability to mediate signal transduction were also studied. We conclude that the C-terminus of delta OR is not essential for plasma membrane targeting, ligand specificity, and agonist-dependent activation. ..