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The role of glucocorticoid receptors in the induction and prevention of hippocampal abnormalities in an animal model of posttraumatic stress disorder

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Abstract

Rationale

Since the precise mechanisms of posttraumatic stress disorder (PTSD) remain unknown, effective treatment interventions have not yet been established. Numerous clinical studies have led to the hypothesis that elevated glucocorticoid levels in response to extreme stress might trigger a pathophysiological cascade which consequently leads to functional and morphological changes in the hippocampus.

Objectives

To elucidate the pathophysiology of PTSD, we examined the alteration of hippocampal gene expression through the glucocorticoid receptor (GR) in the single prolonged stress (SPS) paradigm, a rat model of PTSD.

Methods

We measured nuclear GRs by western blot, and the binding of GR to the promoter of Bcl-2 and Bax genes by chromatin immunoprecipitation-qPCR as well as the expression of these 2 genes by RT-PCR in the hippocampus of SPS rats. In addition, we examined the preventive effects of a GR antagonist on SPS-induced molecular, morphological, and behavioral alterations (hippocampal gene expression of Bcl-2 and Bax, hippocampal apoptosis using TUNEL staining, impaired fear memory extinction (FME) using the contextual fear conditioning paradigm).

Results

Exposure to SPS increased nuclear GR expression and GR binding to Bcl-2 gene, and decreased Bcl-2 mRNA expression. Administration of GR antagonist immediately after SPS prevented activation of the glucocorticoid cascade, hippocampal apoptosis, and impairment FME in SPS rats.

Conclusion

The activation of GRs in response to severe stress may trigger the pathophysiological cascade leading to impaired FME and hippocampal apoptosis. In contrast, administration of GR antagonist could be useful for preventing the development of PTSD.

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References

  • Amos T, Stein DJ, Ipser JC (2014) Pharmacological interventions for preventing post-traumatic stress disorder (PTSD). Cochrane Database Syst Rev 7:Cd006239

  • Birur B, Moore NC, Davis LL (2017) An evidence-based review of early intervention and prevention of posttraumatic stress disorder. Community Ment Health J 53:183–201

    PubMed  Google Scholar 

  • Boe HJ, Holgersen KH, Holen A (2010) Reactivation of posttraumatic stress in male disaster survivors: the role of residual symptoms. J Anxiety Disord 24:397–402

    PubMed  Google Scholar 

  • Bonne O, Vythilingam M, Inagaki M, Wood S, Neumeister A, Nugent AC, Snow J, Luckenbaugh DA, Bain EE, Drevets WC, Charney DS (2008) Reduced posterior hippocampal volume in posttraumatic stress disorder. J Clin Psychiatry 69:1087–1091

    PubMed  PubMed Central  Google Scholar 

  • Bryant RA, Harvey AG, Dang ST, Sackville T, Basten C (1998) Treatment of acute stress disorder: a comparison of cognitive-behavioral therapy and supportive counseling. J Consult Clin Psychol 66:862–866

    CAS  PubMed  Google Scholar 

  • Bryant RA, Sackville T, Dang ST, Moulds M, Guthrie R (1999) Treating acute stress disorder: an evaluation of cognitive behavior therapy and supportive counseling techniques. Am J Psychiatry 156:1780–1786

    CAS  PubMed  Google Scholar 

  • Bryant RA, Moulds ML, Guthrie RM, Nixon RDV (2005) The additive benefit of hypnosis and cognitive-behavioral therapy in treating acute stress disorder. J Consult Clin Psychol 73:334–340

    PubMed  Google Scholar 

  • Bryant RA, Creamer M, O'Donnell M, Silove D, McFarlane AC (2009) A study of the protective function of acute morphine administration on subsequent posttraumatic stress disorder. Biol Psychiatry 65:438–440

    CAS  PubMed  Google Scholar 

  • Committee on the Assessment of Ongoing Efforts in the Treatment of Posttraumatic Stress D, Board on the Health of Select P, Institute of M (2014) Treatment for Posttraumatic Stress Disorder in Military and Veteran Populations: Final Assessment. Washington (DC): National Academies Press (US)

  • Daskalakis NP, Cohen H, Nievergelt CM, Baker DG, Buxbaum JD, Russo SJ, Yehuda R (2016) New translational perspectives for blood-based biomarkers of PTSD: from glucocorticoid to immune mediators of stress susceptibility. Exp Neurol 284:133–140

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dunlop BW, Binder EB, Iosifescu D, Mathew SJ, Neylan TC, Pape JC, Carrillo-Roa T, Green C, Kinkead B, Grigoriadis D, Rothbaum BO, Nemeroff CB, Mayberg HS (2017) Corticotropin-releasing factor receptor 1 antagonism is ineffective for women with posttraumatic stress disorder. Biol Psychiatry 82:866–874

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fanselow MS, Dong HW (2010) Are the dorsal and ventral hippocampus functionally distinct structures? Neuron 65:7–19

    CAS  PubMed  PubMed Central  Google Scholar 

  • Feuer CA, Nishith P, Resick P (2005) Prediction of numbing and effortful avoidance in female rape survivors with chronic PTSD. J Trauma Stress 18:165–170

    PubMed  PubMed Central  Google Scholar 

  • Foa EB, Zoellner LA, Feeny NC (2006) An evaluation of three brief programs for facilitating recovery after assault. J Trauma Stress 19:29–43

    PubMed  Google Scholar 

  • Friedman MJ, Charney DS, Deutch AY (1995) Neurobiological and clinical consequences of stress: from normal adaptation to post-traumatic stress disorder. Lippincott Williams & Wilkins Publishers, Philadelphia, PA, US

    Google Scholar 

  • Friedman DP, Aggleton JP, Saunders RC (2002) Comparison of hippocampal, amygdala, and perirhinal projections to the nucleus accumbens: combined anterograde and retrograde tracing study in the macaque brain. J Comp Neurol 450:345–365

    PubMed  Google Scholar 

  • Gao L, Rabbitt EH, Condon JC, Renthal NE, Johnston JM, Mitsche MA, Chambon P, Xu J, O'Malley BW, Mendelson CR (2015) Steroid receptor coactivators 1 and 2 mediate fetal-to-maternal signaling that initiates parturition. J Clin Invest 125:2808–2824

    PubMed  PubMed Central  Google Scholar 

  • Golier JA, Caramanica K, Demaria R, Yehuda R (2012) A pilot study of mifepristone in combat-related PTSD. Depress Res Treat 2012:393251

    PubMed  PubMed Central  Google Scholar 

  • Gruver-Yates AL, Cidlowski JA (2013) Tissue-specific actions of glucocorticoids on apoptosis: a double-edged sword. Cells 2:202–223

    CAS  PubMed  PubMed Central  Google Scholar 

  • Holbrook TL, Galarneau MR, Dye JL, Quinn K, Dougherty AL (2010) Morphine use after combat injury in Iraq and post-traumatic stress disorder. N Engl J Med 362:110–117

    CAS  PubMed  Google Scholar 

  • Hruska B, Cullen PK, Delahanty DL (2014) Pharmacological modulation of acute trauma memories to prevent PTSD: considerations from a developmental perspective. Neurobiol Learn Mem 112:122–129

    CAS  PubMed  Google Scholar 

  • Karst H, Berger S, Erdmann G, Schutz G, Joels M (2010) Metaplasticity of amygdalar responses to the stress hormone corticosterone. Proc Natl Acad Sci U S A 107:14449–14454

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kataoka T, Fuchikami M, Nojima S, Nagashima N, Araki M, Omura J, Miyagi T, Okamoto Y, Morinobu S (2018) Combined brain-derived neurotrophic factor with extinction training alleviate impaired fear extinction in an animal model of post-traumatic stress disorder. Genes Brain Behav 18(7):e12520

  • Keding TJ, Herringa RJ (2015) Abnormal structure of fear circuitry in pediatric post-traumatic stress disorder. Neuropsychopharmacology 40:537–545

    PubMed  Google Scholar 

  • Keller SM, Schreiber WB, Stanfield BR, Knox D (2015) Inhibiting corticosterone synthesis during fear memory formation exacerbates cued fear extinction memory deficits within the single prolonged stress model. Behav Brain Res 287:182–186

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB (1995) Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry 52:1048–1060

    CAS  PubMed  Google Scholar 

  • Kim PJ, Cole MA, Kalman BA, Spencer RL (1998) Evaluation of RU28318 and RU40555 as selective mineralocorticoid receptor and glucocorticoid receptor antagonists, respectively: receptor measures and functional studies. J Steroid Biochem Mol Biol 67:213–222

    CAS  PubMed  Google Scholar 

  • Kitchener P, Di Blasi F, Borrelli E, Piazza PV (2004) Differences between brain structures in nuclear translocation and DNA binding of the glucocorticoid receptor during stress and the circadian cycle. Eur J Neurosci 19:1837–1846

    PubMed  Google Scholar 

  • Knox D, George SA, Fitzpatrick CJ, Rabinak CA, Maren S, Liberzon I (2012) Single prolonged stress disrupts retention of extinguished fear in rats. Learn Mem 19:43–49

    PubMed  PubMed Central  Google Scholar 

  • Kohda K, Harada K, Kato K, Hoshino A, Motohashi J, Yamaji T, Morinobu S, Matsuoka N, Kato N (2007) Glucocorticoid receptor activation is involved in producing abnormal phenotypes of single-prolonged stress rats: a putative post-traumatic stress disorder model. Neuroscience 148:22–33

    CAS  PubMed  Google Scholar 

  • Li X, Han F, Liu D, Shi Y (2010a) Changes of Bax, Bcl-2 and apoptosis in hippocampus in the rat model of post-traumatic stress disorder. Neurol Res 32:579–586

    CAS  PubMed  Google Scholar 

  • Li XM, Han F, Liu DJ, Shi YX (2010b) Single-prolonged stress induced mitochondrial-dependent apoptosis in hippocampus in the rat model of post-traumatic stress disorder. J Chem Neuroanat 40:248–255

    CAS  PubMed  Google Scholar 

  • Liberzon I, Krstov M, Young EA (1997) Stress-restress: effects on ACTH and fast feedback. Psychoneuroendocrinology 22:443–453

    CAS  PubMed  Google Scholar 

  • Liberzon I, Lopez JF, Flagel SB, Vazquez DM, Young EA (1999) Differential regulation of hippocampal glucocorticoid receptors mRNA and fast feedback: relevance to post-traumatic stress disorder. J Neuroendocrinol 11:11–17

    CAS  PubMed  Google Scholar 

  • Litz BT, Gray MJ, Bryant RA, Adler AB (2002) Early intervention for trauma: current status and future directions. Clin Psychol Sci Pract 9:112–134

    Google Scholar 

  • Matsumoto Y, Morinobu S, Yamamoto S, Matsumoto T, Takei S, Fujita Y, Yamawaki S (2013) Vorinostat ameliorates impaired fear extinction possibly via the hippocampal NMDA-CaMKII pathway in an animal model of posttraumatic stress disorder. Psychopharmacology 229:51–62

    CAS  PubMed  Google Scholar 

  • Matsumura K, Noguchi H, Nishi D, Hamazaki K, Hamazaki T, Matsuoka YJ (2017) Effects of omega-3 polyunsaturated fatty acids on psychophysiological symptoms of post-traumatic stress disorder in accident survivors: a randomized, double-blind, placebo-controlled trial. J Affect Disord 224:27–31

    CAS  PubMed  Google Scholar 

  • Matsuoka Y, Nishi D, Hamazaki K, Yonemoto N, Matsumura K, Noguchi H, Hashimoto K, Hamazaki T (2015) Docosahexaenoic acid for selective prevention of posttraumatic stress disorder among severely injured patients: a randomized, placebo-controlled trial. J Clin Psychiatry 76:e1015–e1022

    PubMed  Google Scholar 

  • McGhee LL, Maani CV, Garza TH, Gaylord KM, Black IH (2008) The correlation between ketamine and posttraumatic stress disorder in burned service members. J Trauma 64:S195–S198 discussion S197-8

    CAS  PubMed  Google Scholar 

  • Mifsud KR, Reul JM (2016) Acute stress enhances heterodimerization and binding of corticosteroid receptors at glucocorticoid target genes in the hippocampus. Proc Natl Acad Sci U S A 113:11336–11341

    CAS  PubMed  PubMed Central  Google Scholar 

  • Milad MR, Orr SP, Lasko NB, Chang Y, Rauch SL, Pitman RK (2008) Presence and acquired origin of reduced recall for fear extinction in PTSD: results of a twin study. J Psychiatr Res 42:515–520

    PubMed  PubMed Central  Google Scholar 

  • Milad MR, Pitman RK, Ellis CB, Gold AL, Shin LM, Lasko NB, Zeidan MA, Handwerger K, Orr SP, Rauch SL (2009) Neurobiological basis of failure to recall extinction memory in posttraumatic stress disorder. Biol Psychiatry 66:1075–1082

    PubMed  PubMed Central  Google Scholar 

  • Mitchell JT (1983) When disaster strikes...the critical incident stress debriefing process. JEMS 8:36–39

    CAS  PubMed  Google Scholar 

  • Mocetti P, Silvestrini G, Ballanti P, Patacchioli FR, Di Grezia R, Angelucci L, Bonucci E (2001) Bcl-2 and Bax expression in cartilage and bone cells after high-dose corticosterone treatment in rats. Tissue Cell 33:1–7

    CAS  PubMed  Google Scholar 

  • Moulton E, Chamness M, Knox D (2018) Characterizing changes in glucocorticoid receptor internalization in the fear circuit in an animal model of post traumatic stress disorder. PLoS One 13:e0205144

    PubMed  PubMed Central  Google Scholar 

  • Necela BM, Cidlowski JA (2004) Mechanisms of glucocorticoid receptor action in noninflammatory and inflammatory cells. Proc Am Thorac Soc 1:239–246

    CAS  PubMed  Google Scholar 

  • Nelson MD, Tumpap AM (2017) Posttraumatic stress disorder symptom severity is associated with left hippocampal volume reduction: a meta-analytic study. CNS Spectrums 22:363–372

    PubMed  Google Scholar 

  • Oakley RH, Cidlowski JA (2013) The biology of the glucocorticoid receptor: new signaling mechanisms in health and disease. J Allergy Clin Immunol 132:1033–1044

    CAS  PubMed  PubMed Central  Google Scholar 

  • O'Doherty DC, Chitty KM, Saddiqui S, Bennett MR, Lagopoulos J (2015) A systematic review and meta-analysis of magnetic resonance imaging measurement of structural volumes in posttraumatic stress disorder. Psychiatry Res 232:1–33

    PubMed  Google Scholar 

  • Paxinos G, Watson C (1998) The Rat Brain in Stereotaxic Coordinates, 4th ed., Academic Press, San Diego

  • Peeters BW, Ruigt GS, Craighead M, Kitchener P (2008) Differential effects of the new glucocorticoid receptor antagonist ORG 34517 and RU486 (mifepristone) on glucocorticoid receptor nuclear translocation in the AtT20 cell line. Ann N Y Acad Sci 1148:536–541

    CAS  PubMed  Google Scholar 

  • Pitman RK, Sanders KM, Zusman RM, Healy AR, Cheema F, Lasko NB, Cahill L, Orr SP (2002) Pilot study of secondary prevention of posttraumatic stress disorder with propranolol. Biol Psychiatry 51:189–192

    CAS  PubMed  Google Scholar 

  • Pitman RK, Milad MR, Igoe SA, Vangel MG, Orr SP, Tsareva A, Gamache K, Nader K (2011) Systemic mifepristone blocks reconsolidation of cue-conditioned fear; propranolol prevents this effect. Behav Neurosci 125:632–638

    PubMed  Google Scholar 

  • Qi W, Gevonden M, Shalev A (2016) Prevention of post-traumatic stress disorder after trauma: current evidence and future directions. Curr Psychiatry Rep 18:20

    PubMed  PubMed Central  Google Scholar 

  • Rao RP, Anilkumar S, McEwen BS, Chattarji S (2012) Glucocorticoids protect against the delayed behavioral and cellular effects of acute stress on the amygdala. Biol Psychiatry 72:466–475

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rothbaum BO, Davis M (2003) Applying learning principles to the treatment of post-trauma reactions. Ann N Y Acad Sci 1008:112–121

    PubMed  Google Scholar 

  • Schelling G, Briegel J, Roozendaal B, Stoll C, Rothenhausler HB, Kapfhammer HP (2001) The effect of stress doses of hydrocortisone during septic shock on posttraumatic stress disorder in survivors. Biol Psychiatry 50:978–985

    CAS  PubMed  Google Scholar 

  • Schelling G, Kilger E, Roozendaal B, de Quervain DJ, Briegel J, Dagge A, Rothenhausler HB, Krauseneck T, Nollert G, Kapfhammer HP (2004) Stress doses of hydrocortisone, traumatic memories, and symptoms of posttraumatic stress disorder in patients after cardiac surgery: a randomized study. Biol Psychiatry 55:627–633

    CAS  PubMed  Google Scholar 

  • Schneier FR, Neria Y, Pavlicova M, Hembree E, Suh EJ, Amsel L, Marshall RD (2012) Combined prolonged exposure therapy and paroxetine for PTSD related to the World Trade Center attack: a randomized controlled trial. Am J Psychiatry 169:80–88

    PubMed  Google Scholar 

  • Shafia S, Vafaei AA, Samaei SA, Bandegi AR, Rafiei A, Valadan R, Hosseini-Khah Z, Mohammadkhani R, Rashidy-Pour A (2017) Effects of moderate treadmill exercise and fluoxetine on behavioural and cognitive deficits, hypothalamic-pituitary-adrenal axis dysfunction and alternations in hippocampal BDNF and mRNA expression of apoptosis - related proteins in a rat model of post-traumatic stress disorder. Neurobiol Learn Mem 139:165–178

    CAS  PubMed  Google Scholar 

  • Siuda D, Wu Z, Chen Y, Guo L, Linke M, Zechner U, Xia N, Reifenberg G, Kleinert H, Forstermann U, Li H (2014) Social isolation-induced epigenetic changes in midbrain of adult mice. J Physiol Pharmacol 65:247–255

    CAS  PubMed  Google Scholar 

  • Souza RR, Noble LJ, McIntyre CK (2017) Using the single prolonged stress model to examine the pathophysiology of PTSD. Front Pharmacol 8:615

    PubMed  PubMed Central  Google Scholar 

  • Spiga F, Knight DM, Droste SK, Conway-Campbell B, Kershaw Y, MacSweeney CP, Thomson FJ, Craighead M, Peeters BW, Lightman SL (2011) Differential effect of glucocorticoid receptor antagonists on glucocorticoid receptor nuclear translocation and DNA binding. J Psychopharmacol (Oxford, England) 25:211–221

    CAS  Google Scholar 

  • Stoddard FJ Jr, Luthra R, Sorrentino EA, Saxe GN, Drake J, Chang Y, Levine JB, Chedekel DS, Sheridan RL (2011) A randomized controlled trial of sertraline to prevent posttraumatic stress disorder in burned children. J Child Adolesc Psychopharmacol 21:469–477

    CAS  PubMed  Google Scholar 

  • Surjit M, Ganti KP, Mukherji A, Ye T, Hua G, Metzger D, Li M, Chambon P (2011) Widespread negative response elements mediate direct repression by agonist-liganded glucocorticoid receptor. Cell 145:224–241

    CAS  PubMed  Google Scholar 

  • Szeszko PR, Lehrner A, Yehuda R (2018) Glucocorticoids and hippocampal structure and function in PTSD. Harv Rev Psychiatry 26:142–157

    PubMed  Google Scholar 

  • Vaiva G, Ducrocq F, Jezequel K, Averland B, Lestavel P, Brunet A, Marmar CR (2003) Immediate treatment with propranolol decreases posttraumatic stress disorder two months after trauma. Biol Psychiatry 54:947–949

    CAS  PubMed  Google Scholar 

  • Wood SH, van Dam S, Craig T, Tacutu R, O’Toole A, Merry BJ, de Magalhães JP (2015) Transcriptome analysis in calorie-restricted rats implicates epigenetic and post-translational mechanisms in neuroprotection and aging. Genome Biol 16:285

    PubMed  PubMed Central  Google Scholar 

  • Yamamoto S, Morinobu S, Fuchikami M, Kurata A, Kozuru T, Yamawaki S (2008) Effects of single prolonged stress and D-cycloserine on contextual fear extinction and hippocampal NMDA receptor expression in a rat model of PTSD. Neuropsychopharmacology 33:2108–2116

    CAS  PubMed  Google Scholar 

  • Yamamoto S, Morinobu S, Takei S, Fuchikami M, Matsuki A, Yamawaki S, Liberzon I (2009) Single prolonged stress: toward an animal model of posttraumatic stress disorder. Depress Anxiety 26:1110–1117

    PubMed  Google Scholar 

  • Yehuda R, Flory JD, Bierer LM, Henn-Haase C, Lehrner A, Desarnaud F, Makotkine I, Daskalakis NP, Marmar CR, Meaney MJ (2015) Lower methylation of glucocorticoid receptor gene promoter 1F in peripheral blood of veterans with posttraumatic stress disorder. Biol Psychiatry 77:356–364

    CAS  PubMed  Google Scholar 

  • Zhang L, Zhou R, Li X, Ursano RJ, Li H (2006) Stress-induced change of mitochondria membrane potential regulated by genomic and non-genomic GR signaling: a possible mechanism for hippocampus atrophy in PTSD. Med Hypotheses 66:1205–1208

    CAS  PubMed  Google Scholar 

  • Zohar J, Yahalom H, Kozlovsky N, Cwikel-Hamzany S, Matar MA, Kaplan Z, Yehuda R, Cohen H (2011) High dose hydrocortisone immediately after trauma may alter the trajectory of PTSD: interplay between clinical and animal studies. Eur Neuropsychopharmacol 21:796–809

    CAS  PubMed  Google Scholar 

  • van Zuiden M, Geuze E, Willemen HL, Vermetten E, Maas M, Amarouchi K, Kavelaars A, Heijnen CJ (2012) Glucocorticoid receptor pathway components predict posttraumatic stress disorder symptom development: a prospective study. Biol Psychiatry 71:309–316

    PubMed  Google Scholar 

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Funding

This work was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI (a grant-in aid for Scientific Research, C) Grant Number JP18K07562, and Takeda Science Foundation.

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Authors and Affiliations

  1. Department of Psychiatry and Neuroscience, Division of Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

    Motoaki Araki, Manabu Fuchikami, Jun Omura, Tatsuhiro Miyagi, Nobuyuki Nagashima & Yasumasa Okamoto

  2. Department of Occupational Therapy, School of Health Science and Social Welfare, Kibi International University, Takahashi, Japan

    Shigeru Morinobu

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  1. Motoaki Araki
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  2. Manabu Fuchikami
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  3. Jun Omura
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  4. Tatsuhiro Miyagi
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  5. Nobuyuki Nagashima
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  6. Yasumasa Okamoto
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  7. Shigeru Morinobu
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Correspondence to Manabu Fuchikami.

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Araki, M., Fuchikami, M., Omura, J. et al. The role of glucocorticoid receptors in the induction and prevention of hippocampal abnormalities in an animal model of posttraumatic stress disorder. Psychopharmacology 237, 2125–2137 (2020). https://doi.org/10.1007/s00213-020-05523-x

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