Skip to main content
SpringerLink
Log in

Differences in 5-HT2A and mGlu2 Receptor Expression Levels and Repressive Epigenetic Modifications at the 5-HT2A Promoter Region in the Roman Low- (RLA-I) and High- (RHA-I) Avoidance Rat Strains

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

The serotonin 2A (5-HT2A) and metabotropic glutamate 2 (mGlu2) receptors regulate each other and are associated with schizophrenia. The Roman high- (RHA-I) and the Roman low- (RLA-I) avoidance rat strains present well-differentiated behavioral profiles, with the RHA-I strain emerging as a putative genetic rat model of schizophrenia-related features. The RHA-I strain shows increased 5-HT2A and decreased mGlu2 receptor binding levels in prefrontal cortex (PFC). Here, we looked for differences in gene expression and transcriptional regulation of these receptors. The striatum (STR) was included in the analysis. 5-HT2A, 5-HT1A, and mGlu2 mRNA and [3H]ketanserin binding levels were measured in brain homogenates. As expected, 5-HT2A binding was significantly increased in PFC in the RHA-I rats, while no difference in binding was observed in STR. Surprisingly, 5-HT2A gene expression was unchanged in PFC but significantly decreased in STR. mGlu2 receptor gene expression was significantly decreased in both PFC and STR. No differences were observed for the 5-HT1A receptor. Chromatin immunoprecipitation assay revealed increased trimethylation of histone 3 at lysine 27 (H3K27me3) at the promoter region of the HTR2A gene in the STR. We further looked at the Akt/GSK3 signaling pathway, a downstream point of convergence of the serotonin and glutamate system, and found increased phosphorylation levels of GSK3β at tyrosine 216 and increased β-catenin levels in the PFC of the RHA-I rats. These results reveal region-specific regulation of the 5-HT2A receptor in the RHA-I rats probably due to absence of mGlu2 receptor that may result in differential regulation of downstream pathways.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Driscoll P, Escorihuela RM, Fernandez-Teruel A, Giorgi O, Schwegler H, Steimer T, Wiersma A, Corda MG et al (1998) Genetic selection and differential stress responses. The Roman lines/strains of rats. Ann N Y Acad Sci 851:501–510

    Article  CAS  PubMed  Google Scholar 

  2. Escorihuela RM, Fernandez-Teruel A, Gil L, Aguilar R, Tobena A, Driscoll P (1999) Inbred Roman high- and low-avoidance rats: differences in anxiety, novelty-seeking, and shuttlebox behaviors. Physiol Behav 67:19–26

    Article  CAS  PubMed  Google Scholar 

  3. Esnal A, Sanchez-Gonzalez A, Rio-Alamos C, Oliveras I, Canete T, Blazquez G, Tobena A, Fernandez-Teruel A (2016) Prepulse inhibition and latent inhibition deficits in Roman high-avoidance vs. Roman low-avoidance rats: modeling schizophrenia-related features. Physiol Behav 163:267–273

    Article  CAS  PubMed  Google Scholar 

  4. Steimer T, Driscoll P (2003) Divergent stress responses and coping styles in psychogenetically selected Roman high-(RHA) and low-(RLA) avoidance rats: behavioural, neuroendocrine and developmental aspects. Stress 6:87–100

    Article  CAS  PubMed  Google Scholar 

  5. Diaz-Moran S, Palencia M, Mont-Cardona C, Canete T, Blazquez G, Martinez-Membrives E, Lopez-Aumatell R, Tobena A et al (2012) Coping style and stress hormone responses in genetically heterogeneous rats: comparison with the Roman rat strains. Behav Brain Res 228:203–210

    Article  CAS  PubMed  Google Scholar 

  6. Giorgi O, Piras G, Corda MG (2007) The psychogenetically selected Roman high- and low-avoidance rat lines: a model to study the individual vulnerability to drug addiction. Neurosci Biobehav Rev 31:148–163

    Article  CAS  PubMed  Google Scholar 

  7. Manzo L, Gomez MJ, Callejas-Aguilera JE, Donaire R, Sabariego M, Fernandez-Teruel A, Canete A, Blazquez G et al (2014) Relationship between ethanol preference and sensation/novelty seeking. Physiol Behav 133:53–60

    Article  CAS  PubMed  Google Scholar 

  8. Moreno M, Cardona D, Gomez MJ, Sanchez-Santed F, Tobena A, Fernandez-Teruel A, Campa L, Sunol C et al (2010) Impulsivity characterization in the Roman high- and low-avoidance rat strains: behavioral and neurochemical differences. Neuropsychopharmacology 35:1198–1208

    Article  PubMed  PubMed Central  Google Scholar 

  9. Klein AB, Ultved L, Adamsen D, Santini MA, Tobena A, Fernandez-Teruel A, Flores P, Moreno M et al (2014) 5-HT(2A) and mGlu2 receptor binding levels are related to differences in impulsive behavior in the Roman low- (RLA) and high- (RHA) avoidance rat strains. Neuroscience 263:36–45

    Article  CAS  PubMed  Google Scholar 

  10. Oliveras I, Rio-Alamos C, Canete T, Blazquez G, Martinez-Membrives E, Giorgi O, Corda MG, Tobena A et al (2015) Prepulse inhibition predicts spatial working memory performance in the inbred Roman high- and low-avoidance rats and in genetically heterogeneous NIH-HS rats: relevance for studying pre-attentive and cognitive anomalies in schizophrenia. Front Behav Neurosci 9:213. doi:10.3389/fnbeh.2015.00213

    Article  PubMed  PubMed Central  Google Scholar 

  11. Luck SJ, Gold JM (2008) The construct of attention in schizophrenia. Biol Psychiatry 64:34–39

    Article  PubMed  PubMed Central  Google Scholar 

  12. Forbes NF, Carrick LA, McIntosh AM, Lawrie SM (2009) Working memory in schizophrenia: a meta-analysis. Psychol Med 39:889–905

    Article  CAS  PubMed  Google Scholar 

  13. Avsar KB, Weller RE, Cox JE, Reid MA, White DM, Lahti AC (2013) An fMRI investigation of delay discounting in patients with schizophrenia. Brain Behav 3:384–401

    Article  PubMed  PubMed Central  Google Scholar 

  14. Weller RE, Avsar KB, Cox JE, Reid MA, White DM, Lahti AC (2014) Delay discounting and task performance consistency in patients with schizophrenia. Psychiatry Res 215:286–293

    Article  PubMed  Google Scholar 

  15. Tan EJ, Rossell SL (2014) Building a neurocognitive profile of thought disorder in schizophrenia using a standardized test battery. Schizophr Res 152:242–245

    Article  CAS  PubMed  Google Scholar 

  16. Barch DM, Cohen R, Csernansky J (2014) Altered cognitive development in the siblings of individuals with schizophrenia. Clinical psychological science : a journal of the Association for Psychological Science 2:138–151

    Article  Google Scholar 

  17. Lecca D, Piras G, Driscoll P, Giorgi O, Corda MG (2004) A differential activation of dopamine output in the shell and core of the nucleus accumbens is associated with the motor responses to addictive drugs: a brain dialysis study in Roman high- and low-avoidance rats. Neuropharmacology 46:688–699

    Article  CAS  PubMed  Google Scholar 

  18. Giorgi O, Lecca D, Piras G, Driscoll P, Corda MG (2003) Dissociation between mesocortical dopamine release and fear-related behaviours in two psychogenetically selected lines of rats that differ in coping strategies to aversive conditions. Eur J Neurosci 17:2716–2726

    Article  CAS  PubMed  Google Scholar 

  19. Tournier BB, Steimer T, Millet P, Moulin-Sallanon M, Vallet P, Ibanez V, Ginovart N (2013) Innately low D2 receptor availability is associated with high novelty-seeking and enhanced behavioural sensitization to amphetamine. Int J Neuropsychopharmacol 16:1819–1834

    Article  CAS  PubMed  Google Scholar 

  20. Giorgi O, Piras G, Lecca D, Hansson S, Driscoll P, Corda MG (2003) Differential neurochemical properties of central serotonergic transmission in Roman high- and low-avoidance rats. J Neurochem 86:422–431

    Article  CAS  PubMed  Google Scholar 

  21. Aznar S, Hervig M (2016) The 5-HT2A serotonin receptor in executive function: implications for neuropsychiatric and neurodegenerative diseases. Neurosci Biobehav Rev 64:63–82

    Article  CAS  PubMed  Google Scholar 

  22. Gonzalez-Maeso J, Weisstaub NV, Zhou M, Chan P, Ivic L, Ang R, Lira A, Bradley-Moore M et al (2007) Hallucinogens recruit specific cortical 5-HT(2A) receptor-mediated signaling pathways to affect behavior. Neuron 53:439–452

    Article  CAS  PubMed  Google Scholar 

  23. Gonzalez-Maeso J, Sealfon SC (2009) Psychedelics and schizophrenia. Trends Neurosci 32:225–232

    Article  CAS  PubMed  Google Scholar 

  24. Ebdrup BH, Rasmussen H, Arnt J, Glenthøj B (2011) Serotonin 2A receptor antagonists for treatment of schizophrenia. Expert Opin Investig Drugs 20:1211–1223

    Article  CAS  PubMed  Google Scholar 

  25. Desamericq G, Schurhoff F, Meary A, Szoke A, Macquin-Mavier I, Bachoud-Levi AC, Maison P (2014) Long-term neurocognitive effects of antipsychotics in schizophrenia: a network meta-analysis. Eur J Clin Pharmacol 70:127–134

    Article  CAS  PubMed  Google Scholar 

  26. Vollenweider FX, Csomor PA, Knappe B, Geyer MA, Quednow BB (2007) The effects of the preferential 5-HT2A agonist psilocybin on prepulse inhibition of startle in healthy human volunteers depend on interstimulus interval. Neuropsychopharmacology 32:1876–1887

    Article  CAS  PubMed  Google Scholar 

  27. Moreno JL, Miranda-Azpiazu P, Garcia-Bea A, Younkin J, Cui M, Kozlenkov A, Ben-Ezra A, Voloudakis G et al (2016) Allosteric signaling through an mGlu2 and 5-HT2A heteromeric receptor complex and its potential contribution to schizophrenia. Sci Signal 9:ra5. doi:10.1126/scisignal.aab0467

    Article  PubMed  PubMed Central  Google Scholar 

  28. Moreno JL, Holloway T, Rayannavar V, Sealfon SC, Gonzalez-Maeso J (2013) Chronic treatment with LY341495 decreases 5-HT(2A) receptor binding and hallucinogenic effects of LSD in mice. Neurosci Lett 536:69–73

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Gonzalez-Maeso J, Ang RL, Yuen T, Chan P, Weisstaub NV, Lopez-Gimenez JF, Zhou M, Okawa Y et al (2008) Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature 452:93–97

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kurita M, Holloway T, Garcia-Bea A, Kozlenkov A, Friedman AK, Moreno JL, Heshmati M, Golden SA et al (2012) HDAC2 regulates atypical antipsychotic responses through the modulation of mGlu2 promoter activity. Nat Neurosci 15:1245–1254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kurita M, Moreno JL, Holloway T, Kozlenkov A, Mocci G, Garcia-Bea A, Hanks JB, Neve R et al (2013) Repressive epigenetic changes at the mGlu2 promoter in frontal cortex of 5-HT2A knockout mice. Mol Pharmacol 83:1166–1175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Sharma RP, Grayson DR, Gavin DP (2008) Histone deactylase 1 expression is increased in the prefrontal cortex of schizophrenia subjects: analysis of the National Brain Databank microarray collection. Schizophr Res 98:111–117

    Article  PubMed  Google Scholar 

  33. Ibi D, Gonzalez-Maeso J (2015) Epigenetic signaling in schizophrenia. Cell Signal 27:2131–2136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Holloway T, Gonzalez-Maeso J (2015) Epigenetic mechanisms of serotonin signaling. ACS Chem Neurosci 6:1099–1109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Akbarian S, Ruehl MG, Bliven E, Luiz LA, Peranelli AC, Baker SP, Roberts RC, Bunney WE Jr et al (2005) Chromatin alterations associated with down-regulated metabolic gene expression in the prefrontal cortex of subjects with schizophrenia. Arch Gen Psychiatry 62:829–840

    Article  CAS  PubMed  Google Scholar 

  36. Abdolmaleky HM, Zhou JR, Thiagalingam S (2015) An update on the epigenetics of psychotic diseases and autism. Epigenomics 7:427–449

    Article  CAS  PubMed  Google Scholar 

  37. Kurita M, Holloway T, Gonzalez-Maeso J (2013) HDAC2 as a new target to improve schizophrenia treatment. Expert Rev Neurother 13:1–3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Goghari VM, Sponheim SR, Macdonald AW III (2010) The functional neuroanatomy of symptom dimensions in schizophrenia: a qualitative and quantitative review of a persistent question. Neurosci Biobehav Rev 34:468–486

    Article  PubMed  Google Scholar 

  39. de Bartolomeis A, Buonaguro EF, Iasevoli F (2013) Serotonin-glutamate and serotonin-dopamine reciprocal interactions as putative molecular targets for novel antipsychotic treatments: from receptor heterodimers to postsynaptic scaffolding and effector proteins. Psychopharmacology 225:1–19

    Article  PubMed  Google Scholar 

  40. Polter AM, Li X (2011) Glycogen synthase kinase-3 is an intermediate modulator of serotonin neurotransmission. Front Mol Neurosci 4:31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Svenningsson P, Tzavara ET, Carruthers R, Rachleff I, Wattler S, Nehls M, McKinzie DL, Fienberg AA et al (2003) Diverse psychotomimetics act through a common signaling pathway. Science 302:1412–1415

    Article  CAS  PubMed  Google Scholar 

  42. Fleige S, Walf V, Huch S, Prgomet C, Sehm J, Pfaffl MW (2006) Comparison of relative mRNA quantification models and the impact of RNA integrity in quantitative real-time RT-PCR. Biotechnol Lett 28:1601–1613

    Article  CAS  PubMed  Google Scholar 

  43. Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J, Kubista M, Mueller R, Nolan T et al (2009) The MIQE guidelines: Minimum Information for Publication of Quantitative Real-Time PCR Experiments. Clin Chem 55:611–622

    Article  CAS  PubMed  Google Scholar 

  44. Huang HS, Matevossian A, Jiang Y, Akbarian S (2006) Chromatin immunoprecipitation in postmortem brain. J Neurosci Methods 156:284–292

    Article  CAS  PubMed  Google Scholar 

  45. Wood CM, Nicolas CS, Choi SL, Roman E, Nylander I, Fernandez-Teruel A, Kiianmaa K, Bienkowski P et al (2016) Prevalence and influence of cys407* Grm2 mutation in Hannover-derived Wistar rats: mGlu2 receptor loss links to alcohol intake, risk taking and emotional behaviour. Neuropharmacology pii S0028-3908(16):30092–30092. doi:10.1016/j.neuropharm

    Google Scholar 

  46. Lopez-Gimenez JF, Mengod G, Palacios JM, Vilaro MT (1997) Selective visualization of rat brain 5-HT2A receptors by autoradiography with [3H]MDL 100,907. Naunyn Schmiedeberg’s Arch Pharmacol 356:446–454

    Article  CAS  Google Scholar 

  47. Erritzoe D, Frokjaer VG, Haugbol S, Marner L, Svarer C, Holst K, Baare WF, Rasmussen PM et al (2009) Brain serotonin 2A receptor binding: relations to body mass index, tobacco and alcohol use. NeuroImage 46:23–30

    Article  CAS  PubMed  Google Scholar 

  48. Wright RA, Johnson BG, Zhang C, Salhoff C, Kingston AE, Calligaro DO, Monn JA, Schoepp DD et al (2013) CNS distribution of metabotropic glutamate 2 and 3 receptors: transgenic mice and [(3)H]LY459477 autoradiography. Neuropharmacology 66:89–98

    Article  CAS  PubMed  Google Scholar 

  49. Delille HK, Mezler M, Marek GJ (2013) The two faces of the pharmacological interaction of mGlu2 and 5-HT(2)A—relevance of receptor heterocomplexes and interaction through functional brain pathways. Neuropharmacology 70:296–305

    Article  CAS  PubMed  Google Scholar 

  50. Levitz J, Habrian C, Bharill S, Fu Z, Vafabakhsh R, Isacoff EY (2016) Mechanism of assembly and cooperativity of homomeric and heteromeric metabotropic glutamate receptors. Neuron 92:143–159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Molinaro G, Traficante A, Riozzi B, Di ML, Curto M, Pallottino S, Nicoletti F, Bruno V et al (2009) Activation of mGlu2/3 metabotropic glutamate receptors negatively regulates the stimulation of inositol phospholipid hydrolysis mediated by 5-hydroxytryptamine2A serotonin receptors in the frontal cortex of living mice. Mol Pharmacol 76:379–387

    Article  CAS  PubMed  Google Scholar 

  52. Moreno JL, Holloway T, Albizu L, Sealfon SC, Gonzalez-Maeso J (2011) Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists. Neurosci Lett 493:76–79

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Grueter BA, Winder DG (2005) Group II and III metabotropic glutamate receptors suppress excitatory synaptic transmission in the dorsolateral bed nucleus of the stria terminalis. Neuropsychopharmacology 30:1302–1311

    Article  CAS  PubMed  Google Scholar 

  54. Santini MA, Ratner C, Aznar S, Klein AB, Knudsen GM, Mikkelsen JD (2013) Enhanced prefrontal serotonin 2A receptor signaling in the subchronic phencyclidine mouse model of schizophrenia. J Neurosci Res 91:634–641

    Article  CAS  PubMed  Google Scholar 

  55. Santini MA, Balu DT, Puhl MD, Hill-Smith TE, Berg AR, Lucki I, Mikkelsen JD, Coyle JT (2014) D-serine deficiency attenuates the behavioral and cellular effects induced by the hallucinogenic 5-HT(2A) receptor agonist DOI. Behav Brain Res 259:242–246

    Article  CAS  PubMed  Google Scholar 

  56. Testa CM, Friberg IK, Weiss SW, Standaert DG (1998) Immunohistochemical localization of metabotropic glutamate receptors mGluR1a and mGluR2/3 in the rat basal ganglia. J Comp Neurol 390:5–19

    Article  CAS  PubMed  Google Scholar 

  57. Carlsson M, Carlsson A (1990) Interactions between glutamatergic and monoaminergic systems within the basal ganglia—implications for schizophrenia and Parkinson’s disease. Trends Neurosci 13:272–276

    Article  CAS  PubMed  Google Scholar 

  58. Carlsson M, Carlsson A (1990) Schizophrenia: a subcortical neurotransmitter imbalance syndrome? Schizophr Bull 16:425–432

    Article  CAS  PubMed  Google Scholar 

  59. Charron A, Hage CE, Servonnet A, Samaha AN (2015) 5-HT2 receptors modulate the expression of antipsychotic-induced dopamine supersensitivity. Eur Neuropsychopharmacol 25:2381–2393

    Article  CAS  PubMed  Google Scholar 

  60. Borroto-Escuela DO, Romero-Fernandez W, Narvaez M, Oflijan J, Agnati LF, Fuxe K (2014) Hallucinogenic 5-HT2AR agonists LSD and DOI enhance dopamine D2R protomer recognition and signaling of D2-5-HT2A heteroreceptor complexes. Biochem Biophys Res Commun 443:278–284

    Article  CAS  PubMed  Google Scholar 

  61. Borroto-Escuela DO, Pintsuk J, Schafer T, Friedland K, Ferraro L, Tanganelli S, Liu F, Fuxe K (2016) Multiple D2 heteroreceptor complexes: new targets for treatment of schizophrenia. Ther Adv Psychopharmacol 6:77–94

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Moreno JL, Kurita M, Holloway T, Lopez J, Cadagan R, Martinez-Sobrido L, Garcia-Sastre A, Gonzalez-Maeso J (2011) Maternal influenza viral infection causes schizophrenia-like alterations of 5-HT(2)A and mGlu(2) receptors in the adult offspring. J Neurosci 31:1863–1872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Kouzarides T (2007) Chromatin modifications and their function. Cell 128:693–705

    Article  CAS  PubMed  Google Scholar 

  64. Zhou VW, Goren A, Bernstein BE (2011) Charting histone modifications and the functional organization of mammalian genomes. Nat Rev Genet 12:7–18

    Article  PubMed  Google Scholar 

  65. Chen Y, Damayanti NP, Irudayaraj J, Dunn K, Zhou FC (2014) Diversity of two forms of DNA methylation in the brain. Front Genet 5:46. doi:10.3389/fgene.2014.00046

    PubMed  PubMed Central  Google Scholar 

  66. Liu H, Chen Y, Lv J, Liu H, Zhu R, Su J, Liu X, Zhang Y et al (2013) Quantitative epigenetic co-variation in CpG islands and co-regulation of developmental genes. Sci Rep 3:2576. doi:10.1038/srep02576

    Article  PubMed  Google Scholar 

  67. Paquette AG, Marsit CJ (2014) The developmental basis of epigenetic regulation of HTR2A and psychiatric outcomes. J Cell Biochem 115:2065–2072

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Paquette AG, Lesseur C, Armstrong DA, Koestler DC, Appleton AA, Lester BM, Marsit CJ (2013) Placental HTR2A methylation is associated with infant neurobehavioral outcomes. Epigenetics 8:796–801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Sutton LP, Rushlow WJ (2011) Regulation of Akt and Wnt signaling by the group II metabotropic glutamate receptor antagonist LY341495 and agonist LY379268. J Neurochem 117:973–983

    Article  CAS  PubMed  Google Scholar 

  70. Jope RS, Johnson GV (2004) The glamour and gloom of glycogen synthase kinase-3. Trends Biochem Sci 29:95–102

    Article  CAS  PubMed  Google Scholar 

  71. Sutton LP, Rushlow WJ (2012) The dopamine D2 receptor regulates Akt and GSK-3 via Dvl-3. Int J Neuropsychopharmacol 15:965–979

  72. Cohen P, Frame S (2001) The renaissance of GSK3. Nat Rev Mol Cell Biol 2:769–776

    Article  CAS  PubMed  Google Scholar 

  73. Pandey GN, Rizavi HS, Tripathi M, Ren X (2015) Region-specific dysregulation of glycogen synthase kinase-3beta and beta-catenin in the postmortem brains of subjects with bipolar disorder and schizophrenia. Bipolar Disord 17:160–171

    Article  CAS  PubMed  Google Scholar 

  74. Kozlovsky N, Belmaker RH, Agam G (2002) GSK-3 and the neurodevelopmental hypothesis of schizophrenia. Eur Neuropsychopharmacol 12:13–25

    Article  CAS  PubMed  Google Scholar 

  75. Ochs SM, Dorostkar MM, Aramuni G, Schon C, Filser S, Poschl J, Kremer A, Van LF et al (2015) Loss of neuronal GSK3beta reduces dendritic spine stability and attenuates excitatory synaptic transmission via beta-catenin. Mol Psychiatry 20:482–489

    Article  CAS  PubMed  Google Scholar 

  76. Maguschak KA, Ressler KJ (2012) The dynamic role of beta-catenin in synaptic plasticity. Neuropharmacology 62:78–88

    Article  CAS  PubMed  Google Scholar 

  77. Mills F, Bartlett TE, Dissing-Olesen L, Wisniewska MB, Kuznicki J, Macvicar BA, Wang YT, Bamji SX (2014) Cognitive flexibility and long-term depression (LTD) are impaired following beta-catenin stabilization in vivo. Proc Natl Acad Sci U S A 111:8631–8636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work has received partial support from grants PSI2013-41872-P (MINECO), 2014SGR-1587 (DGR), and “ICREA-Academia 2013” (to AF-T) and NIH R01MH084894. I.O. is recipient of a PhD FI fellowship (DGR 2014). Travel grants for L.F. were provided by A.P. Moeller Foundation and the Danish Foundation of Medical Science (Fonden til Lægevidenskabens Fremme).

Author information

Authors and Affiliations

  1. Research Laboratory for Stereology and Neuroscience, Bispebjerg and Frederiksberg Hospitals, Building 11B, 2nd floor, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark

    Luna Fomsgaard, Tomasz Brudek, Dea Adamsen & Susana Aznar

  2. Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USA

    Jose L. Moreno, Mario de la Fuente Revenga, Justin Saunders & Javier Gonzalez-Maeso

  3. Departamento de Psiquiatria y Medicina Legal, Instituto de Neurociencias, Universidad Autonoma de Barcelona, Barcelona, Spain

    Cristobal Rio-Alamos, Ignasi Oliveras, Toni Cañete, Gloria Blazquez, Adolf Tobeña & Albert Fernandez-Teruel

  4. Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark

    Anders Bue Klein

Authors
  1. Luna Fomsgaard
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jose L. Moreno
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mario de la Fuente Revenga
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tomasz Brudek
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dea Adamsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Cristobal Rio-Alamos
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Justin Saunders
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Anders Bue Klein
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ignasi Oliveras
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Toni Cañete
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Gloria Blazquez
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Adolf Tobeña
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Albert Fernandez-Teruel
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Javier Gonzalez-Maeso
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Susana Aznar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Susana Aznar.

Ethics declarations

All animals were sacrificed in accordance with the Spanish Royal Decree (RD 53/2013) for the protection of experimental animals and with the European Communities Council Directive (2010/63/EU) at approximately 4 months of age

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fomsgaard, L., Moreno, J.L., de la Fuente Revenga, M. et al. Differences in 5-HT2A and mGlu2 Receptor Expression Levels and Repressive Epigenetic Modifications at the 5-HT2A Promoter Region in the Roman Low- (RLA-I) and High- (RHA-I) Avoidance Rat Strains. Mol Neurobiol 55, 1998–2012 (2018). https://doi.org/10.1007/s12035-017-0457-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-017-0457-y

Keywords

Search

Navigation