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Behavioral and synaptic alterations relevant to obsessive-compulsive disorder in mice with increased EAAT3 expression

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A Correction to this article was published on 21 February 2019

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Abstract

Obsessive-compulsive disorder (OCD) is a severe, chronic neuropsychiatric disorder with a strong genetic component. The SLC1A1 gene encoding the neuronal glutamate transporter EAAT3 has been proposed as a candidate gene for this disorder. Gene variants affecting SLC1A1 expression in human brain tissue have been associated with OCD. Several mouse models fully or partially lacking EAAT3 have shown no alterations in baseline anxiety-like or repetitive behaviors. We generated a transgenic mouse model (EAAT3glo) to achieve conditional, Cre-dependent EAAT3 overexpression and evaluated the overall impact of increased EAAT3 expression at behavioral and synaptic levels. Mice with EAAT3 overexpression driven by CaMKIIα-promoter (EAAT3glo/CMKII) displayed increased anxiety-like and repetitive behaviors that were both restored by chronic, but not acute, treatment with fluoxetine or clomipramine. EAAT3glo/CMKII mice also displayed greater spontaneous recovery of conditioned fear. Electrophysiological and biochemical analyses at corticostriatal synapses of EAAT3glo/CMKII mice revealed changes in NMDA receptor subunit composition and altered NMDA-dependent synaptic plasticity. By recapitulating relevant behavioral, neurophysiological, and psychopharmacological aspects, our results provide support for the glutamatergic hypothesis of OCD, particularly for the increased EAAT3 function, and provide a valuable animal model that may open novel therapeutic approaches to treat this devastating disorder.

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  • 21 February 2019

    The original version of this Article contained an error in the spelling of the author Anna K Radke, which was incorrectly given as Anna R Radke. This has now been corrected in both the PDF and HTML versions of the Article.

References

  1. Murphy DL, Moya PR, Wendland JR, Timpano KR. Genetic contributions to obsessive-compulsive disorder (OCD) and OCD-related disorders. In: Berrettini JNW, (ed). Principles of psychiatric genetics. Cambridge, UK: Cambridge University Press; 2012. p. 121–33.

    Chapter  Google Scholar 

  2. DSM-5. Diagnostic and statistical manual of mental disorders (DSM-5). 5th ed. Alrington, VA: American Psychiatric Association; 2013.

    Google Scholar 

  3. Koran LM, Hanna GL, Hollander E, Nestadt G, Simpson HB, American Psychiatric Association. Practice guideline for the treatment of patients with obsessive-compulsive disorder. Am J Psychiatry. 2007;164:5–53.

    PubMed  Google Scholar 

  4. Ahmari SE, Dougherty DD. Dissecting OCD circuits: from animal models to targeted treatments. Depress Anxiety. 2015;32:550–62.

    Article  Google Scholar 

  5. Pittenger C. Glutamatergic agents for OCD and related disorders. Curr Treat Options Psychiatry. 2015;2:271–83.

    Article  Google Scholar 

  6. Menzies L, Chamberlain SR, Laird AR, Thelen SM, Sahakian BJ, Bullmore ET. Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: the orbitofronto-striatal model revisited. Neurosci Biobehav Rev. 2008;32:525–49.

    Article  Google Scholar 

  7. Rosenberg DR, Hanna GL. Genetic and imaging strategies in obsessive-compulsive disorder: potential implications for treatment development. Biol Psychiatry. 2000;48:1210–22.

    Article  CAS  Google Scholar 

  8. Tian L, Meng C, Jiang Y, Tang Q, Wang S, Xie X, et al. Abnormal functional connectivity of brain network hubs associated with symptom severity in treatment-naive patients with obsessive-compulsive disorder: a resting-state functional MRI study. Prog Neuropsychopharmacol Biol Psychiatry. 2016;66:104–11.

    Article  Google Scholar 

  9. Vaghi MM, Vertes PE, Kitzbichler MG, Apergis-Schoute AM, van der Flier FE, Fineberg NA, et al. Specific frontostriatal circuits for impaired cognitive flexibility and goal-directed planning in obsessive-compulsive disorder: evidence from resting-state functional connectivity. Biol Psychiatry. 2017;81:708–17.

    Article  Google Scholar 

  10. Zike I, Xu T, Hong N, Veenstra-VanderWeele J. Rodent models of obsessive compulsive disorder: evaluating validity to interpret emerging neurobiology. Neuroscience. 2017;345:256–73.

    Article  CAS  Google Scholar 

  11. Bhattacharyya S, Khanna S, Chakrabarty K, Mahadevan A, Christopher R, Shankar SK. Anti-brain autoantibodies and altered excitatory neurotransmitters in obsessive-compulsive disorder. Neuropsychopharmacology. 2009;34:2489–96.

    Article  CAS  Google Scholar 

  12. Chakrabarty K, Bhattacharyya S, Christopher R, Khanna S. Glutamatergic dysfunction in OCD. Neuropsychopharmacology. 2005;30:1735–40.

    Article  CAS  Google Scholar 

  13. Coric V, Taskiran S, Pittenger C, Wasylink S, Mathalon DH, Valentine G, et al. Riluzole augmentation in treatment-resistant obsessive-compulsive disorder: an open-label trial. Biol Psychiatry. 2005;58:424–8.

    Article  CAS  Google Scholar 

  14. Grant P, Lougee L, Hirschtritt M, Swedo SE. An open-label trial of riluzole, a glutamate antagonist, in children with treatment-resistant obsessive-compulsive disorder. J Child Adolesc Psychopharmacol. 2007;17:761–7.

    Article  Google Scholar 

  15. Pittenger C, Krystal JH, Coric V. Glutamate-modulating drugs as novel pharmacotherapeutic agents in the treatment of obsessive-compulsive disorder. NeuroRx. 2006;3:69–81.

    Article  CAS  Google Scholar 

  16. Rodriguez CI, Kegeles LS, Levinson A, Feng T, Marcus SM, Vermes D, et al. Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder: proof-of-concept. Neuropsychopharmacology. 2013;38:2475–83.

    Article  CAS  Google Scholar 

  17. Rodriguez CI, Zwerling J, Kalanthroff E, Shen H, Filippou M, Jo B, et al. Effect of a novel NMDA receptor modulator, rapastinel (Formerly GLYX-13), in OCD: proof of concept. Am J Psychiatry. 2016;173:1239–41.

    Article  Google Scholar 

  18. Nordstrom EJ, Burton FH. A transgenic model of comorbid Tourette’s syndrome and obsessive-compulsive disorder circuitry. Mol Psychiatry. 2002;7:617–25.

    Article  CAS  Google Scholar 

  19. Shmelkov SV, Hormigo A, Jing D, Proenca CC, Bath KG, Milde T, et al. Slitrk5 deficiency impairs corticostriatal circuitry and leads to obsessive-compulsive-like behaviors in mice. Nat Med. 2010;16:598–602.

    Article  CAS  Google Scholar 

  20. Welch JM, Lu J, Rodriguiz RM, Trotta NC, Peca J, Ding JD, et al. Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice. Nature. 2007;448:894–900.

    Article  CAS  Google Scholar 

  21. Dickel DE, Veenstra-VanderWeele J, Cox NJ, Wu X, Fischer DJ, Van Etten-Lee M, et al. Association testing of the positional and functional candidate gene SLC1A1/EAAC1 in early-onset obsessive-compulsive disorder. Arch Gen Psychiatry. 2006;63:778–85.

    Article  CAS  Google Scholar 

  22. Hanna GL, Veenstra-VanderWeele J, Cox NJ, Boehnke M, Himle JA, Curtis GC, et al. Genome-wide linkage analysis of families with obsessive-compulsive disorder ascertained through pediatric probands. Am J Med Genet. 2002;114:541–52.

    Article  Google Scholar 

  23. Arnold PD, Sicard T, Burroughs E, Richter MA, Kennedy JL. Glutamate transporter gene SLC1A1 associated with obsessive-compulsive disorder. Arch Gen Psychiatry. 2006;63:769–76.

    Article  CAS  Google Scholar 

  24. Shugart YY, Wang Y, Samuels JF, Grados MA, Greenberg BD, Knowles JA, et al. A family-based association study of the glutamate transporter gene SLC1A1 in obsessive-compulsive disorder in 378 families. Am J Med Genet B Neuropsychiatr Genet. 2009;150B:886–92.

    Article  CAS  Google Scholar 

  25. Stewart SE, Fagerness JA, Platko J, Smoller JW, Scharf JM, Illmann C, et al. Association of the SLC1A1 glutamate transporter gene and obsessive-compulsive disorder. Am J Med Genet B Neuropsychiatr Genet. 2007;144B:1027–33.

    Article  CAS  Google Scholar 

  26. Veenstra-VanderWeele J, Kim SJ, Gonen D, Hanna GL, Leventhal BL, Cook EH, et al. Genomic organization of the SLC1A1/EAAC1 gene and mutation screening in early-onset obsessive-compulsive disorder. Mol Psychiatry. 2001;6:160–7.

    Article  CAS  Google Scholar 

  27. Wendland JR, Moya PR, Timpano KR, Anavitarte AP, Kruse MR, Wheaton MG, et al. A haplotype containing quantitative trait loci for SLC1A1 gene expression and its association with obsessive-compulsive disorder. Arch Gen Psychiatry. 2009;66:408–16.

    Article  CAS  Google Scholar 

  28. Willour VL, Yao Shugart Y, Samuels J, Grados M, Cullen B, Bienvenu OJ 3rd, et al. Replication study supports evidence for linkage to 9p24 in obsessive-compulsive disorder. Am J Hum Genet. 2004;75:508–13.

    Article  CAS  Google Scholar 

  29. Mattheisen M, Samuels JF, Wang Y, Greenberg BD, Fyer AJ, McCracken JT, et al. Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS. Mol Psychiatry. 2015;20:337–44.

    Article  CAS  Google Scholar 

  30. Stewart SE, Yu D, Scharf JM, Neale BM, Fagerness JA, Mathews CA, et al. Genome-wide association study of obsessive-compulsive disorder. Mol Psychiatry. 2013;18:788–98.

    Article  CAS  Google Scholar 

  31. Kanai Y, Hediger MA. The glutamate/neutral amino acid transporter family SLC1: molecular, physiological and pharmacological aspects. Pflug Arch. 2004;447:469–79.

    Article  CAS  Google Scholar 

  32. Diamond JS. Neuronal glutamate transporters limit activation of NMDA receptors by neurotransmitter spillover on CA1 pyramidal cells. J Neurosci. 2001;21:8328–38.

    Article  CAS  Google Scholar 

  33. Li MH, Underhill SM, Reed C, Phillips TJ, Amara SG, Ingram SL. Amphetamine and methamphetamine increase NMDAR-GluN2B synaptic currents in midbrain dopamine neurons. Neuropsychopharmacology. 2017;42:1539–47.

    Article  CAS  Google Scholar 

  34. Scimemi A, Tian H, Diamond JS. Neuronal transporters regulate glutamate clearance, NMDA receptor activation, and synaptic plasticity in the hippocampus. J Neurosci. 2009;29:14581–95.

    Article  CAS  Google Scholar 

  35. Conti F, DeBiasi S, Minelli A, Rothstein JD, Melone M. EAAC1, a high-affinity glutamate tranporter, is localized to astrocytes and gabaergic neurons besides pyramidal cells in the rat cerebral cortex. Cereb Cortex. 1998;8:108–16.

    Article  CAS  Google Scholar 

  36. Mathews GC, Diamond JS. Neuronal glutamate uptake contributes to GABA synthesis and inhibitory synaptic strength. J Neurosci. 2003;23:2040–8.

    Article  CAS  Google Scholar 

  37. Sepkuty JP, Cohen AS, Eccles C, Rafiq A, Behar K, Ganel R, et al. A neuronal glutamate transporter contributes to neurotransmitter GABA synthesis and epilepsy. J Neurosci. 2002;22:6372–9.

    Article  CAS  Google Scholar 

  38. Underhill SM, Ingram SL, Ahmari SE, Veenstra-VanderWeele J, Amara SG. Neuronal excitatory amino acid transporter EAAT3: emerging functions in health and disease. Neurochem Int. 2018. https://doi.org/10.1016/j.neuint.2018.05.012.

    Article  CAS  Google Scholar 

  39. Gonzalez LF, Henriquez-Belmar F, Delgado-Acevedo C, Cisternas-Olmedo M, Arriagada G, Sotomayor-Zarate R, et al. Neurochemical and behavioral characterization of neuronal glutamate transporter EAAT3 heterozygous mice. Biol Res. 2017;50:29.

    Article  Google Scholar 

  40. Zike ID, Chohan MO, Kopelman JM, Krasnow EN, Flicker D, Nautiyal KM, et al. OCD candidate gene SLC1A1/EAAT3 impacts basal ganglia-mediated activity and stereotypic behavior. Proc Natl Acad Sci USA. 2017;114:5719–24.

    Article  CAS  Google Scholar 

  41. Peghini P, Janzen J, Stoffel W. Glutamate transporter EAAC-1-deficient mice develop dicarboxylic aminoaciduria and behavioral abnormalities but no neurodegeneration. The EMBO Journal 1997;16:3822-32.

    Article  CAS  Google Scholar 

  42. Bradley SV, Hyun TS, Oravecz-Wilson KI, Li L, Waldorff EI, Ermilov AN, et al. Degenerative phenotypes caused by the combined deficiency of murine HIP1 and HIP1r are rescued by human HIP1. Hum Mol Genet. 2007;16:1279–92.

    Article  CAS  Google Scholar 

  43. Jensen AA, Brauner-Osborne H. Pharmacological characterization of human excitatory amino acid transporters EAAT1, EAAT2 and EAAT3 in a fluorescence-based membrane potential assay. Biochem Pharmacol. 2004;67:2115–27.

    Article  CAS  Google Scholar 

  44. Meulendyke KA, Ubaida-Mohien C, Drewes JL, Liao Z, Gama L, Witwer KW, et al. Elevated brain monoamine oxidase activity in SIV- and HIV-associated neurological disease. J Infect Dis. 2014;210:904–12.

    Article  CAS  Google Scholar 

  45. Cho A, Haruyama N, Kulkarni AB. Generation of transgenic mice. Curr Protoc Cell Biol. 2009. https://doi.org/10.1002/0471143030.cb1911s42.

    Article  Google Scholar 

  46. Hall BE, Zheng C, Swaim WD, Cho A, Nagineni CN, Eckhaus MA, et al. Conditional overexpression of TGF-beta1 disrupts mouse salivary gland development and function. Lab Invest. 2010;90:543–55.

    Article  CAS  Google Scholar 

  47. DePoy L, Daut R, Brigman JL, MacPherson K, Crowley N, Gunduz-Cinar O, et al. Chronic alcohol produces neuroadaptations to prime dorsal striatal learning. Proc Natl Acad Sci USA. 2013;110:14783–8.

    Article  CAS  Google Scholar 

  48. Graybeal C, Feyder M, Schulman E, Saksida LM, Bussey TJ, Brigman JL, et al. Paradoxical reversal learning enhancement by stress or prefrontal cortical damage: rescue with BDNF. Nat Neurosci. 2011;14:1507–9.

    Article  CAS  Google Scholar 

  49. Radke AK, Kocharian A, Covey DP, Lovinger DM, Cheer JF, Mateo Y, et al. Contributions of nucleus accumbens dopamine to cognitive flexibility. Eur J Neurosci. 2018. https://doi.org/10.1111/ejn.14152.

  50. Holmseth S, Dehnes Y, Huang YH, Follin-Arbelet VV, Grutle NJ, Mylonakou MN, et al. The density of EAAC1 (EAAT3) glutamate transporters expressed by neurons in the mammalian CNS. J Neurosci. 2012;32:6000–13.

    Article  CAS  Google Scholar 

  51. Watts SD, Torres-Salazar D, Divito CB, Amara SG. Cysteine transport through excitatory amino acid transporter 3 (EAAT3). PLoS One. 2014;9:e109245.

    Article  Google Scholar 

  52. Chamberlain SR, Fineberg NA, Blackwell AD, Robbins TW, Sahakian BJ. Motor inhibition and cognitive flexibility in obsessive-compulsive disorder and trichotillomania. Am J Psychiatry. 2006;163:1282–4.

    Article  Google Scholar 

  53. Gruner P, Pittenger C. Cognitive inflexibility in obsessive-compulsive disorder. Neuroscience. 2017;345:243–55.

    Article  CAS  Google Scholar 

  54. Ahmari SE, Spellman T, Douglass NL, Kheirbek MA, Simpson HB, Deisseroth K, et al. Repeated cortico-striatal stimulation generates persistent OCD-like behavior. Science. 2013;340:1234–9.

    Article  CAS  Google Scholar 

  55. Wan Y, Ade KK, Caffall Z, Ilcim Ozlu M, Eroglu C, Feng G, et al. Circuit-selective striatal synaptic dysfunction in the Sapap3 knockout mouse model of obsessive-compulsive disorder. Biol Psychiatry. 2014;75:623–30.

    Article  CAS  Google Scholar 

  56. Burguiere E, Monteiro P, Mallet L, Feng G, Graybiel AM. Striatal circuits, habits, and implications for obsessive-compulsive disorder. Curr Opin Neurobiol. 2015;30:59–65.

    Article  CAS  Google Scholar 

  57. Paoletti P, Bellone C, Zhou Q. NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease. Nat Rev Neurosci. 2013;14:383–400.

    Article  CAS  Google Scholar 

  58. Yashiro K, Philpot BD. Regulation of NMDA receptor subunit expression and its implications for LTD, LTP, and metaplasticity. Neuropharmacology. 2008;55:1081–94.

    Article  CAS  Google Scholar 

  59. Stewart SE, Mayerfeld C, Arnold PD, Crane JR, O’Dushlaine C, Fagerness JA, et al. Meta-analysis of association between obsessive-compulsive disorder and the 3’ region of neuronal glutamate transporter gene SLC1A1. Am J Med Genet B Neuropsychiatr Genet. 2013;162B:367–79.

    Article  CAS  Google Scholar 

  60. Aoyama K, Suh SW, Hamby AM, Liu J, Chan WY, Chen Y, et al. Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse. Nat Neurosci. 2006;9:119–26.

    Article  CAS  Google Scholar 

  61. Bellini S, Fleming KE, De M, McCauley JP, Petroccione MA, D’Brant LY, et al. Neuronal glutamate transporters control dopaminergic signaling and compulsive behaviors. J Neurosci. 2018;38:937–61.

    Article  CAS  Google Scholar 

  62. Radke AK, Jury NJ, Kocharian A, Marcinkiewcz CA, Lowery-Gionta EG, Pleil KE, et al. Chronic EtOH effects on putative measures of compulsive behavior in mice. Addict Biol. 2017;22:423–34.

    Article  CAS  Google Scholar 

  63. Radke AK, Nakazawa K, Holmes A. Cortical GluN2B deletion attenuates punished suppression of food reward-seeking. Psychopharmacology. 2015;232:3753–61.

    Article  CAS  Google Scholar 

  64. McLaughlin NC, Strong D, Abrantes A, Garnaat S, Cerny A, O’Connell C, et al. Extinction retention and fear renewal in a lifetime obsessive-compulsive disorder sample. Behav Brain Res. 2015;280:72–7.

    Article  CAS  Google Scholar 

  65. Milad MR, Furtak SC, Greenberg JL, Keshaviah A, Im JJ, Falkenstein MJ, et al. Deficits in conditioned fear extinction in obsessive-compulsive disorder and neurobiological changes in the fear circuit. JAMA Psychiatry. 2013;70:608–18.

    Article  Google Scholar 

  66. Reimer AE, de Oliveira AR, Diniz JB, Hoexter MQ, Miguel EC, Milad MR, et al. Fear extinction in an obsessive-compulsive disorder animal model: influence of sex and estrous cycle. Neuropharmacology. 2018;131:104–15.

    Article  CAS  Google Scholar 

  67. Morgan MA, Romanski LM, LeDoux JE. Extinction of emotional learning: contribution of medial prefrontal cortex. Neurosci Lett. 1993;163:109–13.

    Article  CAS  Google Scholar 

  68. Phelps EA, Delgado MR, Nearing KI, LeDoux JE. Extinction learning in humans: role of the amygdala and vmPFC. Neuron. 2004;43:897–905.

    Article  CAS  Google Scholar 

  69. Quirk GJ, Russo GK, Barron JL, Lebron K. The role of ventromedial prefrontal cortex in the recovery of extinguished fear. J Neurosci. 2000;20:6225–31.

    Article  CAS  Google Scholar 

  70. Chamberlain SR, Menzies L, Hampshire A, Suckling J, Fineberg NA, del Campo N, et al. Orbitofrontal dysfunction in patients with obsessive-compulsive disorder and their unaffected relatives. Science. 2008;321:421–2.

    Article  CAS  Google Scholar 

  71. Remijnse PL, Nielen MM, van Balkom AJ, Cath DC, van Oppen P, Uylings HB, et al. Reduced orbitofrontal-striatal activity on a reversal learning task in obsessive-compulsive disorder. Arch Gen Psychiatry. 2006;63:1225–36.

    Article  Google Scholar 

  72. Valerius G, Lumpp A, Kuelz AK, Freyer T, Voderholzer U. Reversal learning as a neuropsychological indicator for the neuropathology of obsessive compulsive disorder? A behavioral study. J Neuropsychiatry Clin Neurosci. 2008;20:210–8.

    Article  Google Scholar 

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Acknowledgements

The authors especially thank Dr. Carla Alvarez and Pedro Espinosa for their work that forms the basis for Figures 4 and 5.

Author information

Author notes

  1. Jens R. Wendland

    Present address: Takeda Pharmaceutical Company Limited, 35 Landsdowne Street, Cambridge, MA, 02139, USA

  2. These authors contributed equally: Claudia Delgado-Acevedo, Sebastián F. Estay.

  3. Dr. Dennis L. Murphy passed away on September 23, 2017.

Authors and Affiliations

  1. Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile

    Claudia Delgado-Acevedo, Angélica P. Escobar, Francisca Henríquez-Belmar, Cristopher A. Reyes, Valentina Haro-Acuña, Ramón Sotomayor-Zárate & Pablo R. Moya

  2. Núcleo Milenio NUMIND Biology of Neuropsychiatric Disorders, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile

    Claudia Delgado-Acevedo, Sebastián F. Estay, Francisca Henríquez-Belmar, Cristopher A. Reyes, Valentina Haro-Acuña, Andrés E. Chávez & Pablo R. Moya

  3. Centro Interdisciplinario de Neurociencias de Valparaíso CINV, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile

    Claudia Delgado-Acevedo, Sebastián F. Estay, Angélica P. Escobar, Andrés E. Chávez & Pablo R. Moya

  4. Instituto de Neurociencias, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile

    Sebastián F. Estay & Andrés E. Chávez

  5. Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD, USA

    Anna K. Radke, Ayesha Sengupta & Andrew Holmes

  6. Department of Psychology and Center for Neuroscience and Behavior, Miami University, Oxford, OH, USA

    Anna K. Radke

  7. Functional Genomics Section and Gene Transfer Core, National Institute of Dental and Craniofacial Research, Bethesda, MD, USA

    Elías Utreras, Andrew Cho & Ashok B. Kulkarni

  8. Department of Biology, Faculty of Sciences, Universidad de Chile, Santiago, Chile

    Elías Utreras

  9. Centro de Neurobiología y Fisiolopatogía Integrativa, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile

    Ramón Sotomayor-Zárate

  10. Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD, USA

    Jens R. Wendland, Dennis L. Murphy & Pablo R. Moya

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  1. Claudia Delgado-Acevedo
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  2. Sebastián F. Estay
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Correspondence to Andrés E. Chávez or Pablo R. Moya.

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Delgado-Acevedo, C., Estay, S.F., Radke, A. et al. Behavioral and synaptic alterations relevant to obsessive-compulsive disorder in mice with increased EAAT3 expression. Neuropsychopharmacol. 44, 1163–1173 (2019). https://doi.org/10.1038/s41386-018-0302-7

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