Gene Symbol: Sigmar1
Description: sigma non-opioid intracellular receptor 1
Alias: Oprs1, Sig1R, sigma1R, sigma non-opioid intracellular receptor 1, opioid receptor, sigma 1, sigma 1 receptor variant SR-1D, sigma 1-type opioid receptor, sigma1-receptor
Species: mouse
Products:     Sigmar1

Top Publications

  1. Navarro G, Moreno E, Aymerich M, Marcellino D, McCormick P, Mallol J, et al. Direct involvement of sigma-1 receptors in the dopamine D1 receptor-mediated effects of cocaine. Proc Natl Acad Sci U S A. 2010;107:18676-81 pubmed publisher
  2. Sabino V, Cottone P, Parylak S, Steardo L, Zorrilla E. Sigma-1 receptor knockout mice display a depressive-like phenotype. Behav Brain Res. 2009;198:472-6 pubmed publisher
    ..The results further suggest that Sig-1Rs inversely modulate depressive-like behavior. ..
  3. Mavlyutov T, Epstein M, Verbny Y, Huerta M, Zaitoun I, Ziskind Conhaim L, et al. Lack of sigma-1 receptor exacerbates ALS progression in mice. Neuroscience. 2013;240:129-34 pubmed publisher
    ..Taken together the data suggest the S1R acts as a brake on excitability, an effect that might enhance longevity in an ALS mouse model. ..
  4. Mavlyutov T, Nickells R, Guo L. Accelerated retinal ganglion cell death in mice deficient in the Sigma-1 receptor. Mol Vis. 2011;17:1034-43 pubmed
    ..Here, we used the ?R1-knockout mouse (Sigmar1(-/-)) to demonstrate unambiguously the role of the ?R1 in protecting the retinal ganglion cells against ..
  5. FONTANILLA D, Johannessen M, Hajipour A, Cozzi N, Jackson M, Ruoho A. The hallucinogen N,N-dimethyltryptamine (DMT) is an endogenous sigma-1 receptor regulator. Science. 2009;323:934-7 pubmed publisher
    ..DMT induced hypermobility in wild-type mice but not in sigma-1 receptor knockout mice. These biochemical, physiological, and behavioral experiments indicate that DMT is an endogenous agonist for the sigma-1 receptor. ..
  6. Hayashi T, SU T. Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca(2+) signaling and cell survival. Cell. 2007;131:596-610 pubmed
    ..These results reveal that the orchestrated ER chaperone machinery at MAM, by sensing ER Ca(2+) concentrations, regulates ER-mitochondrial interorganellar Ca(2+) signaling and cell survival. ..
  7. Hayashi T, SU T. Sigma-1 receptors (sigma(1) binding sites) form raft-like microdomains and target lipid droplets on the endoplasmic reticulum: roles in endoplasmic reticulum lipid compartmentalization and export. J Pharmacol Exp Ther. 2003;306:718-25 pubmed
    ..Thus, sigma-1 receptors are unique endoplasmic reticulum proteins that regulate the compartmentalization of lipids on the endoplasmic reticulum and their export from the endoplasmic reticulum to plasma membrane and c-LDs. ..
  8. Ola M, Moore P, el Sherbeny A, Roon P, Agarwal N, Sarthy V, et al. Expression pattern of sigma receptor 1 mRNA and protein in mammalian retina. Brain Res Mol Brain Res. 2001;95:86-95 pubmed
    ..Our findings suggest that retinal ganglion cells may be amenable to the neuroprotective effects of sigma ligands under conditions of neurotoxicity such as occurs in diabetes. ..
  9. Ha Y, Saul A, Tawfik A, Williams C, Bollinger K, Smith R, et al. Late-onset inner retinal dysfunction in mice lacking sigma receptor 1 (?R1). Invest Ophthalmol Vis Sci. 2011;52:7749-60 pubmed publisher
    ..These data suggest that lack of ?R1 leads to development of late-onset retinal dysfunction with similarities to optic neuropathy. ..

More Information


  1. Shioda N, Ishikawa K, Tagashira H, Ishizuka T, Yawo H, Fukunaga K. Expression of a truncated form of the endoplasmic reticulum chaperone protein, ?1 receptor, promotes mitochondrial energy depletion and apoptosis. J Biol Chem. 2012;287:23318-31 pubmed publisher
    ..Taken together, the newly identified ?(1)SR isoform interferes with ?(1)R function relevant to mitochondrial energy production under ER stress conditions, promoting cellular apoptosis. ..
  2. Kitaichi K, Chabot J, Moebius F, Flandorfer A, Glossmann H, Quirion R. Expression of the purported sigma(1) (sigma(1)) receptor in the mammalian brain and its possible relevance in deficits induced by antagonism of the NMDA receptor complex as revealed using an antisense strategy. J Chem Neuroanat. 2000;20:375-87 pubmed
  3. Cendan C, Pujalte J, Portillo Salido E, Montoliu L, Baeyens J. Formalin-induced pain is reduced in sigma(1) receptor knockout mice. Eur J Pharmacol. 2005;511:73-4 pubmed
    ..In this study we show that both phases of formalin-induced pain were reduced by approximately 55% in sigma1 receptor knockout mice in comparison to wild-type animals...
  4. González Cano R, Merlos M, Baeyens J, Cendan C. ?1 receptors are involved in the visceral pain induced by intracolonic administration of capsaicin in mice. Anesthesiology. 2013;118:691-700 pubmed publisher
    ..These results suggest that ?1 receptors play a role in the mechanisms underlying capsaicin-induced visceral pain and raise novel perspectives for their potential therapeutic value. ..
  5. Sánchez Fernández C, Nieto F, González Cano R, Artacho Cordón A, Romero L, Montilla García Á, et al. Potentiation of morphine-induced mechanical antinociception by ?? receptor inhibition: role of peripheral ?? receptors. Neuropharmacology. 2013;70:348-58 pubmed publisher
    ..These results show that ?? receptor inhibition potentiates morphine-induced mechanical analgesia but not its acute side effects, and that this enhanced analgesia can be induced at peripheral level. ..
  6. de la Puente B, Nadal X, Portillo Salido E, Sánchez Arroyos R, Ovalle S, Palacios G, et al. Sigma-1 receptors regulate activity-induced spinal sensitization and neuropathic pain after peripheral nerve injury. Pain. 2009;145:294-303 pubmed publisher
    ..Our findings identify sigma(1)R as a constituent of the mechanisms modulating activity-induced sensitization in pain pathways and point to sigma(1)R as a new potential target for drugs designed to alleviate neuropathic pain. ..
  7. Jiang G, Mysona B, Dun Y, Gnana Prakasam J, Pabla N, Li W, et al. Expression, subcellular localization, and regulation of sigma receptor in retinal muller cells. Invest Ophthalmol Vis Sci. 2006;47:5576-82 pubmed
    ..Type 1 sigmaR1 (sigmaR1) is expressed in brain oligodendrocytes, but its expression and binding capacity have not been analyzed ..
  8. Langa F, Codony X, Tovar V, Lavado A, Giménez E, Cozar P, et al. Generation and phenotypic analysis of sigma receptor type I (sigma 1) knockout mice. Eur J Neurosci. 2003;18:2188-96 pubmed
    ..The activity of sigma 2-receptors seems to be unaffected in sigma 1-mutant mice. These knockout mice could contribute to better understand the in vivo role of sigma-receptors. ..
  9. Smith S, Duplantier J, Dun Y, Mysona B, Roon P, Martin P, et al. In vivo protection against retinal neurodegeneration by sigma receptor 1 ligand (+)-pentazocine. Invest Ophthalmol Vis Sci. 2008;49:4154-61 pubmed publisher
    To evaluate the neuroprotective properties of the sigma receptor 1 (sigmaR1) ligand, (+)-pentazocine in an in vivo model of retinal neurodegeneration...
  10. Mavlyutov T, Epstein M, Andersen K, Ziskind Conhaim L, Ruoho A. The sigma-1 receptor is enriched in postsynaptic sites of C-terminals in mouse motoneurons. An anatomical and behavioral study. Neuroscience. 2010;167:247-55 pubmed publisher
    ..Together these data indicate that the sigma-1 receptor may play a role in the regulation of motor behavior. ..
  11. Choi S, Roh D, Yoon S, Kwon S, Choi H, Han H, et al. Astrocyte sigma-1 receptors modulate connexin 43 expression leading to the induction of below-level mechanical allodynia in spinal cord injured mice. Neuropharmacology. 2016;111:34-46 pubmed publisher
  12. Kim H, Roh D, Yoon S, Seo H, Kwon Y, Han H, et al. Activation of the spinal sigma-1 receptor enhances NMDA-induced pain via PKC- and PKA-dependent phosphorylation of the NR1 subunit in mice. Br J Pharmacol. 2008;154:1125-34 pubmed publisher
    ..The results of this study suggest that the activation of spinal Sig-1 R enhances NMDA-induced pain via PKC- and PKA-dependent phosphorylation of the NMDA receptor NR 1 subunit. ..
  13. Mei J, Pasternak G. Molecular cloning and pharmacological characterization of the rat sigma1 receptor. Biochem Pharmacol. 2001;62:349-55 pubmed
    In an effort to further understand the pharmacology of sigma receptors, we have cloned the rat homolog of the sigma1 receptor. We isolated a cDNA clone (rs2-2) from rat brain tissue using reverse transcriptase-polymerase chain reaction (..
  14. Ono Y, Tanaka H, Tsuruma K, Shimazawa M, Hara H. A sigma-1 receptor antagonist (NE-100) prevents tunicamycin-induced cell death via GRP78 induction in hippocampal cells. Biochem Biophys Res Commun. 2013;434:904-9 pubmed publisher
    ..These findings suggest that NE-100 suppresses ER stress-induced cell death via CHOP expression by the upregulation of GRP78 through ATF6 pathway, independent sigma-1 receptor antagonist effect. ..
  15. Fukunaga K. [Orphan receptor and chaperon functions of sigma-1 receptor]. Nihon Yakurigaku Zasshi. 2014;143:263-4 pubmed
  16. Zhang Y, Lv X, Bai Y, Zhu X, Wu X, Chao J, et al. Involvement of sigma-1 receptor in astrocyte activation induced by methamphetamine via up-regulation of its own expression. J Neuroinflammation. 2015;12:29 pubmed publisher
    ..Understanding the regulation of σ-1R expression could provide insights into the development of potential therapeutic strategies for astrocyte activation induced by methamphetamine. ..
  17. Francardo V, Bez F, Wieloch T, Nissbrandt H, Ruscher K, Cenci M. Pharmacological stimulation of sigma-1 receptors has neurorestorative effects in experimental parkinsonism. Brain. 2014;137:1998-2014 pubmed publisher
    ..Our results suggest that sigma-1 receptor regulates endogenous defence and plasticity mechanisms in experimental parkinsonism. Boosting the activity of this protein may have disease-modifying effects in Parkinson's disease. ..
  18. King M, Pan Y, Mei J, Chang A, Xu J, Pasternak G. Enhanced kappa-opioid receptor-mediated analgesia by antisense targeting the sigma1 receptor. Eur J Pharmacol. 1997;331:R5-6 pubmed
    In the current study, we used an antisense oligodeoxynucleotide targeting the recently cloned sigma1 receptor to assess its functions within the nervous system. Sigma1 antagonists potentiate the analgesic actions of opioids...
  19. Su J, Hato Yamada N, Araki H, Yoshimura H. Test-retest paradigm of the forced swimming test in female mice is not valid for predicting antidepressant-like activity: participation of acetylcholine and sigma-1 receptors. J Pharmacol Sci. 2013;123:246-55 pubmed
    ..We suggest that the test-retest paradigm in female mice is not adequate for predicting antidepressant-like activity of a drug; the prolongation of immobility in the double FST is modulated through acetylcholine and ?1 receptors. ..
  20. Seth P, Leibach F, Ganapathy V. Cloning and structural analysis of the cDNA and the gene encoding the murine type 1 sigma receptor. Biochem Biophys Res Commun. 1997;241:535-40 pubmed
    ..The gene consists of 4 exons and 3 introns. The 5'-flanking region contains putative binding sites for AP-1, AP-2, GATA-1 and steroid receptors. ..
  21. Geva M, Kusko R, Soares H, Fowler K, Birnberg T, Barash S, et al. Pridopidine activates neuroprotective pathways impaired in Huntington Disease. Hum Mol Genet. 2016;25:3975-3987 pubmed publisher
    ..Since the newly identified pathways are downregulated in neurodegenerative diseases, including HD, these findings suggest that pridopidine may exert neuroprotective effects beyond its role in alleviating some symptoms of HD. ..
  22. Ha Y, Shanmugam A, Markand S, Zorrilla E, Ganapathy V, Smith S. Sigma receptor 1 modulates ER stress and Bcl2 in murine retina. Cell Tissue Res. 2014;356:15-27 pubmed publisher
    ..Data from the analysis of the retinal transcriptome of ?R1 null mice provide new insights into the role of ?R1 in retinal neuroprotection. ..
  23. Sánchez Blázquez P, Rodríguez Muñoz M, Herrero Labrador R, Burgueno J, Zamanillo D, Garzón J. The calcium-sensitive Sigma-1 receptor prevents cannabinoids from provoking glutamate NMDA receptor hypofunction: implications in antinociception and psychotic diseases. Int J Neuropsychopharmacol. 2014;17:1943-55 pubmed publisher
  24. Pan L, Pasternak D, Xu J, Xu M, Lu Z, Pasternak G, et al. Isolation and characterization of alternatively spliced variants of the mouse sigma1 receptor gene, Sigmar1. PLoS ONE. 2017;12:e0174694 pubmed publisher
    The sigma1 receptor acts as a chaperone at the endoplasmic reticulum, associates with multiple proteins in various cellular systems, and involves in a number of diseases, such as addiction, pain, cancer and psychiatric disorders...
  25. Pabba M, Wong A, Ahlskog N, Hristova E, Biscaro D, Nassrallah W, et al. NMDA receptors are upregulated and trafficked to the plasma membrane after sigma-1 receptor activation in the rat hippocampus. J Neurosci. 2014;34:11325-38 pubmed publisher
    ..It also opens new avenues for additional studies into a multitude of pathological conditions in which NMDARs are involved, including schizophrenia, dementia, and stroke. ..
  26. Pal A, FONTANILLA D, Gopalakrishnan A, Chae Y, Markley J, Ruoho A. The sigma-1 receptor protects against cellular oxidative stress and activates antioxidant response elements. Eur J Pharmacol. 2012;682:12-20 pubmed publisher
    ..These novel functions of the sigma-1 receptor were sensitive to well-known sigma ligands via their antagonist/agonist properties. ..
  27. Moon J, Roh D, Yoon S, Choi S, Kwon S, Choi H, et al. σ1 receptors activate astrocytes via p38 MAPK phosphorylation leading to the development of mechanical allodynia in a mouse model of neuropathic pain. Br J Pharmacol. 2014;171:5881-97 pubmed publisher
    ..Spinal σ1 receptors are localized in astrocytes and blockade of σ1 receptors inhibits the pathological activation of astrocytes via modulation of p-p38, which ultimately prevents the development of MA in neuropathic mice. ..
  28. Zhao J, Mysona B, Qureshi A, Kim L, Fields T, Gonsalvez G, et al. (+)-Pentazocine Reduces NMDA-Induced Murine Retinal Ganglion Cell Death Through a σR1-Dependent Mechanism. Invest Ophthalmol Vis Sci. 2016;57:453-61 pubmed publisher
    ..Targeting σR1 activation prevented RGC death while enhancing activation of the mitogen-activated protein kinase (MAPK), ERK1/2. Sigma-1 receptor is a promising therapeutic target for retinal neurodegenerative diseases. ..
  29. Fu Y, Yu S, Guo X, Li X, Li T, Li H, et al. Fluvoxamine increased glutamate release by activating both 5-HT(3) and sigma-1 receptors in prelimbic cortex of chronic restraint stress C57BL/6 mice. Biochim Biophys Acta. 2012;1823:826-37 pubmed publisher
    ..These results suggested that fluvoxamine may have a selective effect and different mechanism based on the condition of animal. ..
  30. Pan Y, Mei J, Xu J, Wan B, Zuckerman A, Pasternak G. Cloning and characterization of a mouse sigma1 receptor. J Neurochem. 1998;70:2279-85 pubmed
    ..HA encodes a high-affinity (+)-[3H]pentazocine binding site with characteristics of a murine sigma1 receptor. An antisense oligodeoxynucleotide designed from S2-1a potentiated opioid analgesia in vivo.
  31. Villard V, Meunier J, Chevallier N, Maurice T. Pharmacological interaction with the sigma1 (?1)-receptor in the acute behavioral effects of antidepressants. J Pharmacol Sci. 2011;115:279-92 pubmed
    ..Moreover, the CFS appears to more reliably uncover a ?(1) pharmacological component in antidepressant screening...
  32. Roh D, Yoon S, Seo H, Kang S, Moon J, Song S, et al. Sigma-1 receptor-induced increase in murine spinal NR1 phosphorylation is mediated by the PKCalpha and epsilon, but not the PKCzeta, isoforms. Neurosci Lett. 2010;477:95-9 pubmed publisher
    ..Conversely, the sigma-1 receptor activation of the PKCzeta isoform appears to be involved in a pain signaling pathway that is independent of spinal pNR1 modulation. ..
  33. Romieu P, Phan V, Martin Fardon R, Maurice T. Involvement of the sigma(1) receptor in cocaine-induced conditioned place preference: possible dependence on dopamine uptake blockade. Neuropsychopharmacology. 2002;26:444-55 pubmed
    ..These results show that strategies targeting the sigma(1) receptor with selective antagonists may allow effective attenuation of cocaine's rewarding properties and, in turn, offer new treatment strategies against drug addiction. ..
  34. Tagashira H, Zhang C, Lu Y, Hasegawa H, Kanai H, Han F, et al. Stimulation of ?1-receptor restores abnormal mitochondrial Ca²? mobilization and ATP production following cardiac hypertrophy. Biochim Biophys Acta. 2013;1830:3082-94 pubmed publisher
    ..Our observations suggest that ?1R stimulation represents a new therapeutic strategy to rescue the heart from hypertrophic dysfunction. ..
  35. Sambo D, Lin M, Owens A, Lebowitz J, Richardson B, Jagnarine D, et al. The sigma-1 receptor modulates methamphetamine dysregulation of dopamine neurotransmission. Nat Commun. 2017;8:2228 pubmed publisher
    ..Broadly, these data provide evidence for σ1R regulation of dopamine neurotransmission and support the σ1R as a putative target for the treatment of methamphetamine addiction. ..
  36. Wang J, Saul A, Cui X, Roon P, Smith S. Absence of Sigma 1 Receptor Accelerates Photoreceptor Cell Death in a Murine Model of Retinitis Pigmentosa. Invest Ophthalmol Vis Sci. 2017;58:4545-4558 pubmed publisher
    Sigma 1 Receptor (Sig1R) is a novel therapeutic target in neurodegenerative diseases, including retinal disease. Sig1R-/- mice have late-onset retinal degeneration with ganglion cell loss that worsens under stress...
  37. Xu Q, Ji X, Chi T, Liu P, Jin G, Chen L, et al. Sigma-1 receptor in brain ischemia/reperfusion: Possible role in the NR2A-induced pathway to regulate brain-derived neurotrophic factor. J Neurol Sci. 2017;376:166-175 pubmed publisher
    ..The activation of σ1r improves the impairment of learning and memory in the ischemia/reperfusion model, and the expression of BDNF, which may have been achieved through the NR2A-CaMKIV-TORC1 pathway. ..
  38. Seth P, Ganapathy M, Conway S, Bridges C, Smith S, Casellas P, et al. Expression pattern of the type 1 sigma receptor in the brain and identity of critical anionic amino acid residues in the ligand-binding domain of the receptor. Biochim Biophys Acta. 2001;1540:59-67 pubmed
    The type 1 sigma receptor (sigmaR1) has been shown to participate in a variety of functions in the central nervous system...
  39. Shen K, Zhang Y, Lv X, Chen X, Zhou R, Nguyen L, et al. Molecular Mechanisms Involving Sigma-1 Receptor in Cell Apoptosis of BV-2 Microglial Cells Induced by Methamphetamine. CNS Neurol Disord Drug Targets. 2016;15:857-65 pubmed
    ..Understanding the link between ? -1R and apoptosis will lead to development of therapeutic strategies targeting methamphetamine-mediated microglial death/dysfunction. ..
  40. Hiramatsu M, Hoshino T. Involvement of kappa-opioid receptors and sigma receptors in memory function demonstrated using an antisense strategy. Brain Res. 2004;1030:247-55 pubmed
    ..We have recently reported that the memory improving effect of (-)-pentazocine was antagonized by sigma1 receptor antagonist...
  41. Johannessen M, Ramachandran S, Riemer L, Ramos Serrano A, Ruoho A, Jackson M. Voltage-gated sodium channel modulation by sigma-receptors in cardiac myocytes and heterologous systems. Am J Physiol Cell Physiol. 2009;296:C1049-57 pubmed publisher
    ..The modulation of Na(v)1.5 channels by sigma-receptors in the heart suggests an important pathway by which drugs can alter cardiac excitability and rhythmicity. ..
  42. Tejada M, Montilla García Á, Sánchez Fernández C, Entrena J, Perazzoli G, Baeyens J, et al. Sigma-1 receptor inhibition reverses acute inflammatory hyperalgesia in mice: role of peripheral sigma-1 receptors. Psychopharmacology (Berl). 2014;231:3855-69 pubmed publisher
    ..1 receptors play a major role in inflammatory hyperalgesia. Targeting ?1 receptors in the inflamed tissue may be useful for the treatment of inflammatory pain. ..
  43. Kourrich S, Hayashi T, Chuang J, Tsai S, SU T, Bonci A. Dynamic interaction between sigma-1 receptor and Kv1.2 shapes neuronal and behavioral responses to cocaine. Cell. 2013;152:236-47 pubmed publisher
    ..Functional consequences of Sig-1R binding to K(+) channels may have implications for other chronic diseases where maladaptive intrinsic plasticity and Sig-1Rs are engaged. ..
  44. Shanmugam A, Wang J, Markand S, Perry R, Tawfik A, Zorrilla E, et al. Sigma receptor 1 activation attenuates release of inflammatory cytokines MIP1γ, MIP2, MIP3α, and IL12 (p40/p70) by retinal Müller glial cells. J Neurochem. 2015;132:546-58 pubmed publisher
    ..The findings suggest that release of certain inflammatory cytokines by Müller cells can be attenuated by σR1 ligands providing insights into the retinal neuroprotective role of this receptor. ..
  45. Mishina M, Ishiwata K, Ishii K, Kitamura S, Kimura Y, Kawamura K, et al. Function of sigma1 receptors in Parkinson's disease. Acta Neurol Scand. 2005;112:103-7 pubmed
    ..Release of dopamine is reduced asymmetrically in the putamen of early PD. [11C]SA4503 PET is an indicator of presynaptic dopaminergic damage in PD. ..
  46. Wang J, Shanmugam A, Markand S, Zorrilla E, Ganapathy V, Smith S. Sigma 1 receptor regulates the oxidative stress response in primary retinal Müller glial cells via NRF2 signaling and system xc(-), the Na(+)-independent glutamate-cystine exchanger. Free Radic Biol Med. 2015;86:25-36 pubmed publisher
    ..The neuroprotective role of σ1R may be linked directly to the oxidative stress-mediating properties of supportive glial cells. ..
  47. Zhang S, Hong J, Zhang T, Wu J, Chen L. Activation of Sigma-1 Receptor Alleviates Postpartum Estrogen Withdrawal-Induced "Depression" Through Restoring Hippocampal nNOS-NO-CREB Activities in Mice. Mol Neurobiol. 2017;54:3017-3030 pubmed publisher
    ..The findings indicate that the activation of ?1R can alleviate postpartum "depression" through increasing nNOS-NO-CREB activities. ..
  48. Vollrath J, Sechi A, Dreser A, Katona I, Wiemuth D, Vervoorts J, et al. Loss of function of the ALS protein SigR1 leads to ER pathology associated with defective autophagy and lipid raft disturbances. Cell Death Dis. 2014;5:e1290 pubmed publisher
    ..Taken together, our results support the notion that loss of SigR1 function contributes to ALS pathology by causing abnormal ER morphology, lipid raft destabilization and defective endolysosomal pathways. ..
  49. Wang J, Cui X, Roon P, Smith S. Role of Sigma 1 Receptor in Retinal Degeneration of the Ins2Akita/+ Murine Model of Diabetic Retinopathy. Invest Ophthalmol Vis Sci. 2016;57:2770-81 pubmed publisher
    Sigma receptor 1 (Sigma1R), a nonopioid putative molecular chaperone, has neuroprotective properties in retina...
  50. Mei J, Pasternak G. Sigma1 receptor modulation of opioid analgesia in the mouse. J Pharmacol Exp Ther. 2002;300:1070-4 pubmed
    Opioid analgesia is influenced by many factors, including the sigma1 receptor system. Current studies show the importance of supraspinal mechanisms in these sigma1actions...
  51. Chevallier N, Keller E, Maurice T. Behavioural phenotyping of knockout mice for the sigma-1 (??) chaperone protein revealed gender-related anxiety, depressive-like and memory alterations. J Psychopharmacol. 2011;25:960-75 pubmed publisher
    ..protein invalidation therefore affected stress or anxiety response but not memory in males. Changes in steroid tonus in female animals led, however, to memory impairments that increased with age. ..
  52. Ito K, Hirooka Y, Matsukawa R, Nakano M, Sunagawa K. Decreased brain sigma-1 receptor contributes to the relationship between heart failure and depression. Cardiovasc Res. 2012;93:33-40 pubmed publisher
    ..These results indicate that decreased brain S1R contributes to the relationship between heart failure and depression in a mouse model of pressure overload. ..
  53. Ha Y, Saul A, Tawfik A, Zorrilla E, Ganapathy V, Smith S. Diabetes accelerates retinal ganglion cell dysfunction in mice lacking sigma receptor 1. Mol Vis. 2012;18:2860-70 pubmed
    ..The data support the hypothesis that ?R1 plays a key role in modulating retinal stress and may be an important target for retinal disease. ..