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Gene Review

Oprd1  -  opioid receptor, delta 1

Rattus norvegicus

Synonyms: D-OR-1, DOR-1, Delta-type opioid receptor, Opioid receptor A, Ror-a
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Disease relevance of Oprd1

  • Whereas an AS ODN probe directed against the KOR3/ORL-1 clone produced small (36%), but significant reductions in 2DG-induced hyperphagia, an AS ODN probe directed against the DOR-1 clone was ineffective [1].
  • In contrast to HPC-induced increase in DADLE binding density, prolonged hypoxia caused severe neuronal injury with a significant decrease in DADLE binding density and DOR mRNA level [2].
  • Long-term treatment with ethanol increases delta-opioid receptor (DOR) expression in the NG108-15 neuroblastoma x glioma hybrid cell line [3].
  • The specific role of the Delta opioid receptor (DOR), in opioid-induced respiratory depression in the ventral respiratory group (VRG) is largely unknown [4].
  • These results indicate that DOR in the MPO, particularly in the MPNm, plays an important role in the regulation of lordosis [5].

High impact information on Oprd1

  • There is also synergy between DOR or CB1 with ethanol, another addicting agent [6].
  • Here we determine the role of dopamine D2 receptors (D2) in PKA signaling responses to delta-opioid (DOR) and cannabinoid (CB1) receptors [6].
  • Thirty-five percent of DOR labeling was observed within dendrites and dendritic spines [7].
  • In axons and terminals, DOR labeling was distributed along plasma and vesicular membranes [7].
  • The shell compartment of the nucleus accumbens (AcbSh) is prominently involved in the rewarding aspects of delta-opioid receptor (DOR) agonists, including one of its putative endogenous ligands, Met5-enkephalin (Enk) [7].

Chemical compound and disease context of Oprd1

  • In comparison with delta-opioid receptor (DOR)-induced protection in DIV20 neurons exposed to 72 h of hypoxia, glycine-induced protection was weaker than that of DOR but stronger than that of GABA and taurine [8].
  • In this study we examined the effects of the DOR agonist, (+)-4-[(alpha R)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethyl-benzamide (SNC80), on behavioral seizures and hippocampal histopathology in the pilocarpine model of temporal lobe epilepsy [9].
  • [D-Pen(2), D-Pen(5)]-enkephalin (DPDPE), a DOR agonist, microinfused into the MPO, 52-54h after EB-priming, inhibited lordosis when compared with the aCSF (vehicle) control (P <== 0.05) [5].

Biological context of Oprd1

  • In VGLUT1-positive pyramidal cells, weak DOR but no MOR gene expression was detected [10].
  • The deduced amino acid sequence (372 aa) closely resembles the murine delta-opioid receptor, DOR-1 [11].
  • In contrast, CAR induced a distinct downregulation in DOR- and KOR-LIs [12].
  • After induction of unilateral paw inflammation, mRNA content for DOR remained unchanged, but a bi-phasic upregulation for MOR mRNA with an early peak at 1-2 h and a late increase at 96 h was found in ipsilateral DRG [13].
  • The ODN targeting the DOR nucleotide sequence 280 - 299 (aODN280 - 299, exon 2), decreased brain delta-opioid receptor density significantly more than aODNs targeting exon 1 (aODN239 - 258), exon 2 (aODN361 - 380), or exon 3 (aODN741 - 760) (to 52% vs 79, 72, and 68%) [14].

Anatomical context of Oprd1


Associations of Oprd1 with chemical compounds

  • Expression of high DOR mRNA levels was restricted to GAD-positive neurons in the principal cell layers, oriens layer and hilus [10].
  • This was carried out by combining immunocytochemical staining for MOR1, DOR1, and serotonin with fluorescent retrograde tract-tracing [17].
  • No changes in the levels of mRNA for DOR were detected after exposure to cocaine in the brain regions examined [18].
  • Following microinjection of DAMGO into the PAG, either the highly selective DOR antagonist TIPP[psi] or the DOR2 antagonist naltriben (NTB) was microinjected into the RVM [19].
  • Although SH caused a decrease in DOR expression and neuronal injury, HPC induced an increase in DOR mRNA and protein levels and reversed the reduction in levels of the endogenous DOR peptide, leucine enkephalin, normally seen during SH, thus protecting the neurons from SH insult [20].

Regulatory relationships of Oprd1


Other interactions of Oprd1

  • DOR1 immunostaining patterns revealed primarily a postsynaptic localization of the receptor in pallidal cell bodies adjacent to enkephalin- or synaptophysin-positive fiber terminals [22].
  • To examine whether this increase is related to transcription, the mRNA of Delta- (DOR) and mu-opioid receptor (MOR) in lumbar DRG was quantified by real time Light Cycler polymerase chain reaction (LC-PCR), and correlated to ligand binding in DRG and sciatic nerve [13].

Analytical, diagnostic and therapeutic context of Oprd1

  • Protein and mRNA levels of DOR were detected by receptor binding and RT-PCR, respectively [2].
  • In the present study, we examined the expression of DOR1 and MOR1 mRNAs in PAG neurons projecting to RVM using quantitative in situ hybridization and retrograde tract-tracing [23].
  • To specifically address the relative pre- and postsynaptic contribution to spinal opioid analgesia, we have quantitatively assessed the pre- vs. postsynaptic distribution of the mu-opioid (MOR-1, MOP(1)) and delta-opioid receptors (DOR-1, DOP(1)) [24].
  • Two immunoreactive bands were seen on Western blots of brainstem lysates for both MOR (50 and 70 kDa) and DOR (30 and 60 kDa) [25].
  • We confirmed the changes in expression for the genes encoding the nuclear protein prothymosin(alpha) and the delta-1 opioid receptor (DOR1) by Northern blotting or in situ hybridization [26].


  1. Antisense mapping of opioid receptor clones: effects upon 2-deoxy-D-glucose-induced hyperphagia. Burdick, K., Yu, W.Z., Ragnauth, A., Moroz, M., Pan, Y.X., Rossi, G.C., Pasternak, G.W., Bodnar, R.J. Brain Res. (1998) [Pubmed]
  2. Rapid hypoxia preconditioning protects cortical neurons from glutamate toxicity through delta-opioid receptor. Zhang, J., Qian, H., Zhao, P., Hong, S.S., Xia, Y. Stroke (2006) [Pubmed]
  3. Ethanol increases delta-opioid receptor gene expression in neuronal cell lines. Charness, M.E., Hu, G., Edwards, R.H., Querimit, L.A. Mol. Pharmacol. (1993) [Pubmed]
  4. Presynaptic delta opioid receptors differentially modulate rhythm and pattern generation in the ventral respiratory group of the rat. Lonergan, T., Goodchild, A.K., Christie, M.J., Pilowsky, P.M. Neuroscience (2003) [Pubmed]
  5. Medial preoptic area delta-opioid receptors inhibit lordosis. Sinchak, K., Mills, R.H., Eckersell, C.B., Micevych, P.E. Behav. Brain Res. (2004) [Pubmed]
  6. Addicting drugs utilize a synergistic molecular mechanism in common requiring adenosine and Gi-beta gamma dimers. Yao, L., Fan, P., Jiang, Z., Mailliard, W.S., Gordon, A.S., Diamond, I. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  7. Cellular sites for activation of delta-opioid receptors in the rat nucleus accumbens shell: relationship with Met5-enkephalin. Svingos, A.L., Clarke, C.L., Pickel, V.M. J. Neurosci. (1998) [Pubmed]
  8. GABA and glycine are protective to mature but toxic to immature rat cortical neurons under hypoxia. Zhao, P., Qian, H., Xia, Y. Eur. J. Neurosci. (2005) [Pubmed]
  9. The delta opioid receptor agonist, SNC80, has complex, dose-dependent effects on pilocarpine-induced seizures in Sprague-Dawley rats. Bausch, S.B., Garland, J.P., Yamada, J. Brain Res. (2005) [Pubmed]
  10. Neuronal types expressing mu- and delta-opioid receptor mRNA in the rat hippocampal formation. Stumm, R.K., Zhou, C., Schulz, S., Höllt, V. J. Comp. Neurol. (2004) [Pubmed]
  11. Molecular cloning and expression of a delta-opioid receptor from rat brain. Abood, M.E., Noel, M.A., Farnsworth, J.S., Tao, Q. J. Neurosci. Res. (1994) [Pubmed]
  12. Expression of mu-, delta-, and kappa-opioid receptor-like immunoreactivities in rat dorsal root ganglia after carrageenan-induced inflammation. Ji, R.R., Zhang, Q., Law, P.Y., Low, H.H., Elde, R., Hökfelt, T. J. Neurosci. (1995) [Pubmed]
  13. Rapid upregulation of mu opioid receptor mRNA in dorsal root ganglia in response to peripheral inflammation depends on neuronal conduction. Puehler, W., Zöllner, C., Brack, A., Shaqura, M.A., Krause, H., Schäfer, M., Stein, C. Neuroscience (2004) [Pubmed]
  14. Effects of antisense oligonucleotides on brain delta-opioid receptor density and on SNC80-induced locomotor stimulation and colonic transit inhibition in rats. Negri, L., Broccardo, M., Lattanzi, R., Melchiorri, P. Br. J. Pharmacol. (1999) [Pubmed]
  15. Delta-opioid receptor-immunoreactive neurons in the rat cranial sensory ganglia. Ichikawa, H., Schulz, S., Höllt, V., Sugimoto, T. Brain Res. (2005) [Pubmed]
  16. The presence of opioid receptors in rat inner ear. Jongkamonwiwat, N., Phansuwan-Pujito, P., Sarapoke, P., Chetsawang, B., Casalotti, S.O., Forge, A., Dodson, H., Govitrapong, P. Hear. Res. (2003) [Pubmed]
  17. mu-Opioid and delta-opioid receptors are expressed in brainstem antinociceptive circuits: studies using immunocytochemistry and retrograde tract-tracing. Kalyuzhny, A.E., Arvidsson, U., Wu, W., Wessendorf, M.W. J. Neurosci. (1996) [Pubmed]
  18. Effect of chronic cocaine treatment on mu- and delta-opioid receptor mRNA levels in dopaminergically innervated brain regions. Azaryan, A.V., Coughlin, L.J., Búzás, B., Clock, B.J., Cox, B.M. J. Neurochem. (1996) [Pubmed]
  19. Highly delta selective antagonists in the RVM attenuate the antinociceptive effect of PAG DAMGO. Hirakawa, N., Tershner, S.A., Fields, H.L. Neuroreport (1999) [Pubmed]
  20. Oxygen-sensitive {delta}-opioid receptor-regulated survival and death signals: novel insights into neuronal preconditioning and protection. Ma, M.C., Qian, H., Ghassemi, F., Zhao, P., Xia, Y. J. Biol. Chem. (2005) [Pubmed]
  21. Equal proportions of small and large DRG neurons express opioid receptor mRNAs. Wang, H., Wessendorf, M.W. J. Comp. Neurol. (2001) [Pubmed]
  22. Presynaptic versus postsynaptic localization of mu and delta opioid receptors in dorsal and ventral striatopallidal pathways. Olive, M.F., Anton, B., Micevych, P., Evans, C.J., Maidment, N.T. J. Neurosci. (1997) [Pubmed]
  23. Mu- and delta-opioid receptor mRNAs are expressed in periaqueductal gray neurons projecting to the rostral ventromedial medulla. Wang, H., Wessendorf, M.W. Neuroscience (2002) [Pubmed]
  24. Mu and delta opioid receptor-like immunoreactivity in the cervical spinal cord of the rat after dorsal rhizotomy or neonatal capsaicin: an analysis of pre- and postsynaptic receptor distributions. Abbadie, C., Lombard, M.C., Besson, J.M., Trafton, J.A., Basbaum, A.I. Brain Res. (2002) [Pubmed]
  25. Developmental expression of mu and delta opioid receptors in the rat brainstem: evidence for a postnatal switch in micro isoform expression. Kivell, B.M., Day, D.J., McDonald, F.J., Miller, J.H. Brain Res. Dev. Brain Res. (2004) [Pubmed]
  26. Hippocampal gene expression profiling in spatial discrimination learning. Robles, Y., Vivas-Mejía, P.E., Ortiz-Zuazaga, H.G., Félix, J., Ramos, X., Peña de Ortiz, S. Neurobiology of learning and memory. (2003) [Pubmed]
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