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Stress-Induced Deficits in Cognition and Emotionality: A Role for Glutamate

Part of the Current Topics in Behavioral Neurosciences book series (CTBN,volume 12)

Abstract

Stress is associated with a number of neuropsychiatric disorders, many of which are characterized by altered cognition and emotionality. Rodent models of stress have shown parallel behavioral changes such as impaired working memory, cognitive flexibility and fear extinction. This coincides with morphological changes to pyramidal neurons in the prefrontal cortex, hippocampus and amygdala, key cortical regions mediating these behaviors. Increasing evidence suggests that alteration in the function of the glutamatergic system may contribute to the pathology seen in neuropsychiatric disorders. Stress can alter glutamate transmission in the prefrontal cortex, hippocampus and amygdala and altered glutamate transmission has been linked to neuronal morphological changes. More recently, genetic manipulations in rodent models have allowed for subunit-specific analysis of the role of AMPA and NMDA receptors as well as glutamate transporters in behaviors shown to be altered by stress. Together these data point to a role for glutamate in mediating the cognitive and emotional changes observed in neuropsychiatric disorders. Furthering our understanding of how stress affects glutamate receptors and related signaling pathways will ultimately contribute to the development of improved therapeutics for individuals suffering from neuropsychiatric disorders.

Keywords

  • Glutamate
  • Stress
  • Emotionality
  • Cognition

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References

  • Anderson CM, Swanson RA (2000) Astrocyte glutamate transport: review of properties, regulation, and physiological functions. Glia 32:1–14

    PubMed  CAS  Google Scholar 

  • Arnsten AF (2009) Stress signalling pathways that impair prefrontal cortex structure and function. Nat Rev Neurosci 10:410–422

    PubMed  CAS  Google Scholar 

  • Arriza JL, Fairman WA, Wadiche JI, Murdoch GH, Kavanaugh MP, Amara SG (1994) Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex. J Neurosci 14:5559–5569

    PubMed  CAS  Google Scholar 

  • Baran SE, Armstrong CE, Niren DC, Hanna JJ, Conrad CD (2009) Chronic stress and sex differences on the recall of fear conditioning and extinction. Neurobiol Learn Mem 91:323–332

    PubMed  Google Scholar 

  • Bauer D, Gupta D, Harotunian V, Meador-Woodruff JH, McCullumsmith RE (2008) Abnormal expression of glutamate transporter and transporter interacting molecules in prefrontal cortex in elderly patients with schizophrenia. Schizophr Res 104:108–120

    PubMed  Google Scholar 

  • Belforte JE, Zsiros V, Sklar ER, Jiang Z, Yu G, Li Y, Quinlan EM, Nakazawa K (2010) Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes. Nat Neurosci 13:76–83

    PubMed  CAS  Google Scholar 

  • Berton O, McClung CA, Dileone RJ, Krishnan V, Renthal W, Russo SJ, Graham D, Tsankova NM, Bolanos CA, Rios M, Monteggia LM, Self DW, Nestler EJ (2006) Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science 311:864–868

    PubMed  CAS  Google Scholar 

  • Bird CM, Burgess N (2008) The hippocampus and memory: insights from spatial processing. Nat Rev Neurosci 9:182–194

    PubMed  CAS  Google Scholar 

  • Blechert J, Michael T, Vriends N, Margraf J, Wilhelm FH (2007) Fear conditioning in posttraumatic stress disorder: evidence for delayed extinction of autonomic, experiential, and behavioural responses. Behav Res Ther 45:2019–2033

    PubMed  Google Scholar 

  • Bondi CO, Rodriguez G, Gould GG, Frazer A, Morilak DA (2008) Chronic unpredictable stress induces a cognitive deficit and anxiety-like behavior in rats that is prevented by chronic antidepressant drug treatment. Neuropsychopharmacology 33:320–331

    PubMed  CAS  Google Scholar 

  • Boyce-Rustay JM, Holmes A (2006) Genetic inactivation of the NMDA receptor NR2A subunit has anxiolytic- and antidepressant-like effects in mice. Neuropsychopharmacology 31:2405–2414

    PubMed  CAS  Google Scholar 

  • Brigman JL, Wright T, Talani G, Prasad-Mulcare S, Jinde S, Seabold GK, Mathur P, Davis MI, Bock R, Gustin RM, Colbran RJ, Alvarez VA, Nakazawa K, Delpire E, Lovinger DM, Holmes A (2010) Loss of GluN2B-containing NMDA receptors in CA1 hippocampus and cortex impairs long-term depression, reduces dendritic spine density, and disrupts learning. J Neurosci 30:4590–4600

    PubMed  CAS  Google Scholar 

  • Brown SM, Henning S, Wellman CL (2005) Mild, short-term stress alters dendritic morphology in rat medial prefrontal cortex. Cereb Cortex 15:1714–1722

    PubMed  Google Scholar 

  • Campbell AM, Park CR, Zoladz PR, Munoz C, Fleshner M, Diamond DM (2008) Pre-training administration of tianeptine, but not propranolol, protects hippocampus-dependent memory from being impaired by predator stress. Eur Neuropsychopharmacol 18:87–98

    PubMed  CAS  Google Scholar 

  • Carvalho AL, Caldeira MV, Santos SD, Duarte CB (2008) Role of the brain-derived neurotrophic factor at glutamatergic synapses. Br J Pharmacol 153(1):S310–S324

    PubMed  CAS  Google Scholar 

  • Cerqueira JJ, Mailliet F, Almeida OF, Jay TM, Sousa N (2007) The prefrontal cortex as a key target of the maladaptive response to stress. J Neurosci 27:2781–2787

    PubMed  CAS  Google Scholar 

  • Cerqueira JJ, Pego JM, Taipa R, Bessa JM, Almeida OF, Sousa N (2005) Morphological correlates of corticosteroid-induced changes in prefrontal cortex-dependent behaviors. J Neurosci 25:7792–7800

    PubMed  CAS  Google Scholar 

  • Choudary PV, Molnar M, Evans SJ, Tomita H, Li JZ, Vawter MP, Myers RM, Bunney WE Jr, Akil H, Watson SJ, Jones EG (2005) Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression. Proc Natl Acad Sci USA 102:15653–15658

    PubMed  CAS  Google Scholar 

  • Chudasama Y, Robbins TW (2006) Functions of frontostriatal systems in cognition: comparative neuropsychopharmacological studies in rats, monkeys and humans. Biol Psychol 73:19–38

    PubMed  CAS  Google Scholar 

  • Ciabarra AM, Sullivan JM, Gahn LG, Pecht G, Heinemann S, Sevarino KA (1995) Cloning and characterization of chi-1: a developmentally regulated member of a novel class of the ionotropic glutamate receptor family. J Neurosci 15:6498–6508

    PubMed  CAS  Google Scholar 

  • Conboy L, Tanrikut C, Zoladz PR, Campbell AM, Park CR, Gabriel C, Mocaer E, Sandi C, Diamond DM (2009) The antidepressant agomelatine blocks the adverse effects of stress on memory and enables spatial learning to rapidly increase neural cell adhesion molecule (NCAM) expression in the hippocampus of rats. Int J Neuropsychopharmacol 12:329–341

    PubMed  CAS  Google Scholar 

  • Corcoran KA, Quirk GJ (2007) Activity in prelimbic cortex is necessary for the expression of learned, but not innate, fears. J Neurosci 27:840–844

    PubMed  CAS  Google Scholar 

  • Cravens CJ, Vargas-Pinto N, Christian KM, Nakazawa K (2006) CA3 NMDA receptors are crucial for rapid and automatic representation of context memory. Eur J Neurosci 24:1771–1780

    PubMed  Google Scholar 

  • Czeh B, Muller-Keuker JI, Rygula R, Abumaria N, Hiemke C, Domenici E, Fuchs E (2007) Chronic social stress inhibits cell proliferation in the adult medial prefrontal cortex: hemispheric asymmetry and reversal by fluoxetine treatment. Neuropsychopharmacology 32:1490–1503

    PubMed  CAS  Google Scholar 

  • Dalley JW, Cardinal RN, Robbins TW (2004) Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates. Neurosci Biobehav Rev 28:771–784

    PubMed  CAS  Google Scholar 

  • de Kloet ER, Joels M, Holsboer F (2005) Stress and the brain: from adaptation to disease. Nat Rev Neurosci 6:463–475

    PubMed  Google Scholar 

  • Diamond DM, Park CR, Heman KL, Rose GM (1999) Exposing rats to a predator impairs spatial working memory in the radial arm water maze. Hippocampus 9:542–552

    PubMed  CAS  Google Scholar 

  • Dias-Ferreira E, Sousa JC, Melo I, Morgado P, Mesquita AR, Cerqueira JJ, Costa RM, Sousa N (2009) Chronic stress causes frontostriatal reorganization and affects decision-making. Science 325:621–625

    PubMed  CAS  Google Scholar 

  • Dirnagl U, Iadecola C, Moskowitz MA (1999) Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci 22:391–397

    PubMed  CAS  Google Scholar 

  • Eiland L, McEwen BS (2012) Early life stress followed by subsequent adult chronic stress potentiates anxiety and blunts hippocampal structural remodeling. Hippocampus 22(1):82–91

    PubMed  Google Scholar 

  • Engert F, Bonhoeffer T (1999) Dendritic spine changes associated with hippocampal long-term synaptic plasticity. Nature 399:66–70

    PubMed  CAS  Google Scholar 

  • Ferreri F, Lapp LK, Peretti CS (2011) Current research on cognitive aspects of anxiety disorders. Curr Opin Psychiatry 24(1):49–54

    PubMed  Google Scholar 

  • Feyissa AM, Chandran A, Stockmeier CA, Karolewicz B (2009) Reduced levels of NR2A and NR2B subunits of NMDA receptor and PSD-95 in the prefrontal cortex in major depression. Prog Neuropsychopharmacol Biol Psychiatry 33:70–75

    PubMed  CAS  Google Scholar 

  • Fitzgerald PJ, Barkus C, Feyder M, Wiedholz LM, Chen YC, Karlsson RM, Machado-Vieira R, Graybeal C, Sharp T, Zarate C, Harvey-White J, Du J, Sprengel R, Gass P, Bannerman D, Holmes A (2010) Does gene deletion of AMPA GluA1 phenocopy features of schizoaffective disorder? Neurobiol Dis 40(3):608–621

    PubMed  CAS  Google Scholar 

  • Fumagalli E, Funicello M, Rauen T, Gobbi M, Mennini T (2008) Riluzole enhances the activity of glutamate transporters GLAST, GLT1 and EAAC1. Eur J Pharmacol 578:171–176

    PubMed  CAS  Google Scholar 

  • Garrett JE, Kim I, Wilson RE, Wellman CL (2006) Effect of N-methyl-d-aspartate receptor blockade on plasticity of frontal cortex after cholinergic deafferentation in rat. Neuroscience 140:57–66

    PubMed  CAS  Google Scholar 

  • Goldwater DS, Pavlides C, Hunter RG, Bloss EB, Hof PR, McEwen BS, Morrison JH (2009) Structural and functional alterations to rat medial prefrontal cortex following chronic restraint stress and recovery. Neuroscience 164:798–808

    PubMed  CAS  Google Scholar 

  • Gourley SL, Kedves AT, Olausson P, Taylor JR (2009) A history of corticosterone exposure regulates fear extinction and cortical NR2B, GluR2/3, and BDNF. Neuropsychopharmacology 34(3):707–716

    PubMed  CAS  Google Scholar 

  • Gourley SL, Kiraly DD, Howell JL, Olausson P, Taylor JR (2008) Acute Hippocampal Brain-Derived Neurotrophic Factor Restores Motivational and Forced Swim Performance After Corticosterone. Biol Psychiatry 64(10):884–890

    PubMed  CAS  Google Scholar 

  • Govindarajan A, Rao BS, Nair D, Trinh M, Mawjee N, Tonegawa S, Chattarji S (2006) Transgenic brain-derived neurotrophic factor expression causes both anxiogenic and antidepressant effects. Proc Natl Acad Sci USA 103:13208–13213

    PubMed  CAS  Google Scholar 

  • Halene TB, Ehrlichman RS, Liang Y, Christian EP, Jonak GJ, Gur TL, Blendy JA, Dow HC, Brodkin ES, Schneider F, Gur RC, Siegel SJ (2009) Assessment of NMDA receptor NR1 subunit hypofunction in mice as a model for schizophrenia. Genes Brain Behav 8:661–675

    PubMed  CAS  Google Scholar 

  • Hammen C (2005) Stress and depression. Annu Rev Clin Psychol 1:293–319

    PubMed  Google Scholar 

  • Hardingham GE, Bading H (2003) The Yin and Yang of NMDA receptor signalling. Trends Neurosci 26(2):81–89

    PubMed  CAS  Google Scholar 

  • Hassel B, Iversen EG, Gjerstad L, Tauboll E (2001) Up-regulation of hippocampal glutamate transport during chronic treatment with sodium valproate. J Neurochem 77:1285–1292

    PubMed  CAS  Google Scholar 

  • Holmes A, le Guisquet AM, Vogel E, Millstein RA, Leman S, Belzung C (2005) Early life genetic, epigenetic and environmental factors shaping emotionality in rodents. Neurosci Biobehav Rev 29:1335–1346

    PubMed  Google Scholar 

  • Holmes A, Wellman CL (2009) Stress-induced prefrontal reorganization and executive dysfunction in rodents. Neurosci Biobehav Rev 33:773–783

    PubMed  Google Scholar 

  • Huerta PT, Sun LD, Wilson MA, Tonegawa S (2000) Formation of temporal memory requires NMDA receptors within CA1 pyramidal neurons. Neuron 25:473–480

    PubMed  CAS  Google Scholar 

  • Huot RL, Thrivikraman KV, Meaney MJ, Plotsky PM (2001) Development of adult ethanol preference and anxiety as a consequence of neonatal maternal separation in Long Evans rats and reversal with antidepressant treatment. Psychopharmacology (Berl) 158:366–373

    CAS  Google Scholar 

  • Izquierdo A, Wellman CL, Holmes A (2006) Brief uncontrollable stress causes dendritic retraction in infralimbic cortex and resistance to fear extinction in mice. J Neurosci 26:5733–5738

    PubMed  CAS  Google Scholar 

  • Ji J, Maren S (2007) Hippocampal involvement in contextual modulation of fear extinction. Hippocampus 17:749–758

    PubMed  Google Scholar 

  • Joels M, Karst H, Alfarez D, Heine VM, Qin Y, van Riel E, Verkuyl M, Lucassen PJ, Krugers HJ (2004) Effects of chronic stress on structure and cell function in rat hippocampus and hypothalamus. Stress 7:221–231

    PubMed  CAS  Google Scholar 

  • Joels M, Karst H, Krugers HJ, Lucassen PJ (2007) Chronic stress: implications for neuronal morphology, function and neurogenesis. Front Neuroendocrinol 28:72–96

    PubMed  Google Scholar 

  • Judo C, Matsumoto M, Yamazaki D, Hiraide S, Yanagawa Y, Kimura S, Shimamura K, Togashi H (2010) Early stress exposure impairs synaptic potentiation in the rat medial prefrontal cortex underlying contextual fear extinction. Neuroscience 169:1705–1714

    PubMed  CAS  Google Scholar 

  • Karlsson RM, Heilig M, Holmes A (2008) Loss of Glial Glutamate and Aspartate Transporter (Excitatory Amino Acid Transporter 1) Causes Locomotor Hyperactivity and Exaggerated Responses to Psychotomimetics: Rescue by Haloperidol and Metabotropic Glutamate 2/3 Agonist. Biol Psychiatry 64(9):810–814

    PubMed  CAS  Google Scholar 

  • Karlsson RM, Tanaka K, Saksida LM, Bussey TJ, Heilig M, Holmes A (2009) Assessment of glutamate transporter GLAST (EAAT1)-deficient mice for phenotypes relevant to the negative and executive/cognitive symptoms of schizophrenia. Neuropsychopharmacology 34(6):1578–1589

    PubMed  CAS  Google Scholar 

  • Kim JJ, Foy MR, Thompson RF (1996) Behavioral stress modifies hippocampal plasticity through N-methyl-D-aspartate receptor activation. Proc Natl Acad Sci USA 93:4750–4753

    PubMed  CAS  Google Scholar 

  • Kim JJ, Lee HJ, Han JS, Packard MG (2001) Amygdala is critical for stress-induced modulation of hippocampal long-term potentiation and learning. J Neurosci 21:5222–5228

    PubMed  CAS  Google Scholar 

  • Kiselycznyk C, Svenningsson P, Delpire E, Holmes A (2011) Genetic, pharmacological, and lesion analyses reveal a selective role for corticohippocampal GLUN2B in a novel repeated swim stress paradigm. Neuroscience 193:259–268

    PubMed  CAS  Google Scholar 

  • Kole MH, Costoli T, Koolhaas JM, Fuchs E (2004) Bidirectional shift in the cornu ammonis 3 pyramidal dendritic organization following brief stress. Neuroscience 125:337–347

    PubMed  CAS  Google Scholar 

  • Kuczewski N, Porcher C, Lessmann V, Medina I, Gaiarsa JL (2009) Activity-dependent dendritic release of BDNF and biological consequences. Mol Neurobiol 39:37–49

    PubMed  CAS  Google Scholar 

  • Lapiz-Bluhm MD, Soto-Pina AE, Hensler JG, Morilak DA (2009) Chronic intermittent cold stress and serotonin depletion induce deficits of reversal learning in an attentional set-shifting test in rats. Psychopharmacology (Berl) 202:329–341

    CAS  Google Scholar 

  • Law AJ, Deakin JF (2001) Asymmetrical reductions of hippocampal NMDAR1 glutamate receptor mRNA in the psychoses. Neuroreport 12:2971–2974

    PubMed  CAS  Google Scholar 

  • Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M, Li XY, Aghajanian G, Duman RS (2010) mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 329:959–964

    PubMed  CAS  Google Scholar 

  • Lipton SA, Rosenberg PA (1994) Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med 330:613–622

    PubMed  CAS  Google Scholar 

  • Liston C, Miller MM, Goldwater DS, Radley JJ, Rocher AB, Hof PR, Morrison JH, McEwen BS (2006) Stress-induced alterations in prefrontal cortical dendritic morphology predict selective impairments in perceptual attentional set-shifting. J Neurosci 26:7870–7874

    PubMed  CAS  Google Scholar 

  • Lu B (2003) BDNF and activity-dependent synaptic modulation. Learn Mem 10:86–98

    PubMed  Google Scholar 

  • Lupien SJ, McEwen BS, Gunnar MR, Heim C (2009) Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat Rev Neurosci 10:434–445

    PubMed  CAS  Google Scholar 

  • Magarinos AM, McEwen BS (1995) Stress-induced atrophy of apical dendrites of hippocampal CA3c neurons: comparison of stressors. Neuroscience 69:83–88

    PubMed  CAS  Google Scholar 

  • Maren S, Holt W (2000) The hippocampus and contextual memory retrieval in Pavlovian conditioning. Behav Brain Res 110:97–108

    PubMed  CAS  Google Scholar 

  • Maren S, Quirk GJ (2004) Neuronal signalling of fear memory. Nat Rev Neurosci 5:844–852

    PubMed  CAS  Google Scholar 

  • Martin KP, Wellman CL (2011). NMDA receptor blockade alters stress-induced dendritic remodeling in medial prefrontal cortex. Cereb Cortex 21(10):2366–2373

    PubMed  Google Scholar 

  • Matsuzaki M, Honkura N, Ellis-Davies GC, Kasai H (2004) Structural basis of long-term potentiation in single dendritic spines. Nature 429:761–766

    PubMed  CAS  Google Scholar 

  • McCullumsmith RE, Meador-Woodruff JH (2002) Striatal excitatory amino acid transporter transcript expression in schizophrenia, bipolar disorder, and major depressive disorder. Neuropsychopharmacology 26:368–375

    PubMed  CAS  Google Scholar 

  • McEwen BS (2000a) Allostasis and allostatic load: implications for neuropsychopharmacology. Neuropsychopharmacology 22:108–124

    PubMed  CAS  Google Scholar 

  • McEwen BS (2000b) The neurobiology of stress: from serendipity to clinical relevance. Brain Res 886:172–189

    PubMed  CAS  Google Scholar 

  • McEwen BS (2001) Plasticity of the hippocampus: adaptation to chronic stress and allostatic load. Ann N Y Acad Sci 933:265–277

    PubMed  CAS  Google Scholar 

  • McLean A, Dowson J, Toone B, Young S, Bazanis E, Robbins TW, Sahakian BJ (2004) Characteristic neurocognitive profile associated with adult attention-deficit/hyperactivity disorder. Psychol Med 34:681–692

    PubMed  CAS  Google Scholar 

  • Michael T, Blechert J, Vriends N, Margraf J, Wilhelm FH (2007) Fear conditioning in panic disorder: Enhanced resistance to extinction. J Abnorm Psychol 116:612–617

    PubMed  Google Scholar 

  • Miracle AD, Brace MF, Huyck KD, Singler SA, Wellman CL (2006) Chronic stress impairs recall of extinction of conditioned fear. Neurobiol Learn Mem 85:213–218

    PubMed  Google Scholar 

  • Mizoguchi K, Yuzurihara M, Ishige A, Sasaki H, Chui DH, Tabira T (2000) Chronic stress induces impairment of spatial working memory because of prefrontal dopaminergic dysfunction. J Neurosci 20:1568–1574

    PubMed  CAS  Google Scholar 

  • Moghaddam B (1993) Stress preferentially increases extraneuronal levels of excitatory amino acids in the prefrontal cortex: comparison to hippocampus and basal ganglia. J Neurochem 60:1650–1657

    PubMed  CAS  Google Scholar 

  • Mozhui K, Karlsson RM, Kash TL, Ihne J, Norcross M, Patel S, Farrell MR, Hill EE, Graybeal C, Martin KP, Camp M, Fitzgerald PJ, Ciobanu DC, Sprengel R, Mishina M, Wellman CL, Winder DG, Williams RW, Holmes A (2010) Strain differences in stress responsivity are associated with divergent amygdala gene expression and glutamate-mediated neuronal excitability. J Neurosci 30:5357–5367

    PubMed  CAS  Google Scholar 

  • Murphy FC, Michael A, Robbins TW, Sahakian BJ (2003) Neuropsychological impairment in patients with major depressive disorder: the effects of feedback on task performance. Psychol Med 33:455–467

    PubMed  CAS  Google Scholar 

  • Murray GK, Cheng F, Clark L, Barnett JH, Blackwell AD, Fletcher PC, Robbins TW, Bullmore ET, Jones PB (2008) Reinforcement and reversal learning in first-episode psychosis. Schizophr Bull 34:848–855

    PubMed  CAS  Google Scholar 

  • Myers KM, Davis M (2007) Mechanisms of fear extinction. Mol Psychiatry 12:120–150

    PubMed  CAS  Google Scholar 

  • Nibuya M, Morinobu S, Duman RS (1995) Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci 15:7539–7547

    PubMed  CAS  Google Scholar 

  • Olney JW, Collins RC, Sloviter RS (1986) Excitotoxic mechanisms of epileptic brain damage. Adv Neurol 44:857–877

    PubMed  CAS  Google Scholar 

  • Pare D, Quirk GJ, Ledoux JE (2004) New vistas on amygdala networks in conditioned fear. J Neurophysiol 92:1–9

    PubMed  Google Scholar 

  • Park CR, Zoladz PR, Conrad CD, Fleshner M, Diamond DM (2008) Acute predator stress impairs the consolidation and retrieval of hippocampus-dependent memory in male and female rats. Learn Mem 15:271–280

    PubMed  Google Scholar 

  • Pego JM, Morgado P, Pinto LG, Cerqueira JJ, Almeida OF, Sousa N (2008) Dissociation of the morphological correlates of stress-induced anxiety and fear. Eur J Neurosci 27:1503–1516

    PubMed  CAS  Google Scholar 

  • Pittenger C, Duman RS (2008) Stress, depression, and neuroplasticity: a convergence of mechanisms. Neuropsychopharmacology 33:88–109

    PubMed  CAS  Google Scholar 

  • Quirk GJ, Mueller D (2008) Neural mechanisms of extinction learning and retrieval. Neuropsychopharmacology 33:56–72

    PubMed  Google Scholar 

  • Radley JJ, Rocher AB, Miller M, Janssen WG, Liston C, Hof PR, McEwen BS, Morrison JH (2006) Repeated stress induces dendritic spine loss in the rat medial prefrontal cortex. Cereb Cortex 16:313–320

    PubMed  Google Scholar 

  • Radley JJ, Rocher AB, Rodriguez A, Ehlenberger DB, Dammann M, McEwen BS, Morrison JH, Wearne SL, Hof PR (2008) Repeated stress alters dendritic spine morphology in the rat medial prefrontal cortex. J Comp Neurol 507:1141–1150

    PubMed  Google Scholar 

  • Radley JJ, Sisti HM, Hao J, Rocher AB, McCall T, Hof PR, McEwen BS, Morrison JH (2004) Chronic behavioral stress induces apical dendritic reorganization in pyramidal neurons of the medial prefrontal cortex. Neuroscience 125:1–6

    PubMed  CAS  Google Scholar 

  • Rao VL, Dogan A, Bowen KK, Todd KG, Dempsey RJ (2001a) Antisense knockdown of the glial glutamate transporter GLT-1 exacerbates hippocampal neuronal damage following traumatic injury to rat brain. Eur J Neurosci 13:119–128

    PubMed  CAS  Google Scholar 

  • Rao VL, Dogan A, Todd KG, Bowen KK, Kim BT, Rothstein JD, Dempsey RJ (2001b) Antisense knockdown of the glial glutamate transporter GLT-1, but not the neuronal glutamate transporter EAAC1, exacerbates transient focal cerebral ischemia-induced neuronal damage in rat brain. J Neurosci 21:1876–1883

    PubMed  CAS  Google Scholar 

  • Rau V, DeCola JP, Fanselow MS (2005) Stress-induced enhancement of fear learning: an animal model of posttraumatic stress disorder. Neurosci Biobehav Rev 29:1207–1223

    PubMed  Google Scholar 

  • Robbins TW (2007) Shifting and stopping: fronto-striatal substrates, neurochemical modulation and clinical implications. Philos Trans R Soc Lond B Biol Sci 362:917–932

    PubMed  CAS  Google Scholar 

  • Rodrigues SM, LeDoux JE, Sapolsky RM (2009) The influence of stress hormones on fear circuitry. Annu Rev Neurosci 32:289–313

    PubMed  CAS  Google Scholar 

  • Rogers MA, Kasai K, Koji M, Fukuda R, Iwanami A, Nakagome K, Fukuda M, Kato N (2004) Executive and prefrontal dysfunction in unipolar depression: a review of neuropsychological and imaging evidence. Neurosci Res 50:1–11

    PubMed  Google Scholar 

  • Roozendaal B, McEwen BS, Chattarji S (2009) Stress, memory and the amygdala. Nat Rev Neurosci 10(6):423–433

    PubMed  CAS  Google Scholar 

  • Rosenmund C, Stern-Bach Y, Stevens CF (1998) The tetrameric structure of a glutamate receptor channel. Science 280:1596–1599

    PubMed  CAS  Google Scholar 

  • Rothstein JD, Dykes-Hoberg M, Pardo CA, Bristol LA, Jin L, Kuncl RW, Kanai Y, Hediger MA, Wang Y, Schielke JP, Welty DF (1996) Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 16:675–686

    PubMed  CAS  Google Scholar 

  • Sandi C, Merino JJ, Cordero MI, Touyarot K, Venero C (2001) Effects of chronic stress on contextual fear conditioning and the hippocampal expression of the neural cell adhesion molecule, its polysialylation, and L1. Neuroscience 102:329–339

    PubMed  CAS  Google Scholar 

  • Sapolsky RM (2000a) Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry 57:925–935

    PubMed  CAS  Google Scholar 

  • Sapolsky RM (2000b) The possibility of neurotoxicity in the hippocampus in major depression: a primer on neuron death. Biol Psychiatry 48:755–765

    PubMed  CAS  Google Scholar 

  • Schneiderman N, Ironson G, Siegel SD (2005) Stress and health: psychological, behavioral, and biological determinants. Annu Rev Clin Psychol 1:607–628

    PubMed  Google Scholar 

  • Schwabe L, Schachinger H, de Kloet ER, Oitzl MS (2010) Stress impairs spatial but not early stimulus–response learning. Behav Brain Res 213:50–55

    PubMed  Google Scholar 

  • Shansky RM, Morrison JH (2009) Stress-induced dendritic remodeling in the medial prefrontal cortex: effects of circuit, hormones and rest. Brain Res 1293:108–113

    PubMed  CAS  Google Scholar 

  • Shigeri Y, Seal RP, Shimamoto K (2004) Molecular pharmacology of glutamate transporters, EAATs and VGLUTs. Brain Res Brain Res Rev 45:250–265

    PubMed  CAS  Google Scholar 

  • Shirayama Y, Chen AC, Nakagawa S, Russell DS, Duman RS (2002) Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression. J Neurosci 22:3251–3261

    PubMed  CAS  Google Scholar 

  • Sinha R (2008) Chronic stress, drug use, and vulnerability to addiction. Ann N Y Acad Sci 1141:105–130

    PubMed  CAS  Google Scholar 

  • Siuciak JA, Lewis DR, Wiegand SJ, Lindsay RM (1997) Antidepressant-like effect of brain-derived neurotrophic factor (BDNF). Pharmacol Biochem Behav 56:131–137

    PubMed  CAS  Google Scholar 

  • Smith RE, Haroutunian V, Davis KL, Meador-Woodruff JH (2001) Vesicular glutamate transporter transcript expression in the thalamus in schizophrenia. Neuroreport 12:2885–2887

    PubMed  CAS  Google Scholar 

  • Sokolov BP (1998) Expression of NMDAR1, GluR1, GluR7, and KA1 glutamate receptor mRNAs is decreased in frontal cortex of “neuroleptic-free” schizophrenics: evidence on reversible up-regulation by typical neuroleptics. J Neurochem 71:2454–2464

    PubMed  CAS  Google Scholar 

  • Sousa N, Lukoyanov NV, Madeira MD, Almeida OF, Paula-Barbosa MM (2000) Reorganization of the morphology of hippocampal neurites and synapses after stress-induced damage correlates with behavioral improvement. Neuroscience 97:253–266

    PubMed  CAS  Google Scholar 

  • Sterner EY, Kalynchuk LE (2010) Behavioral and neurobiological consequences of prolonged glucocorticoid exposure in rats: relevance to depression. Prog Neuropsychopharmacol Biol Psychiatry 34:777–790

    PubMed  CAS  Google Scholar 

  • Svenningsson P, Bateup H, Qi H, Takamiya K, Huganir RL, Spedding M, Roth BL, McEwen BS, Greengard P (2007) Involvement of AMPA receptor phosphorylation in antidepressant actions with special reference to tianeptine. Eur J Neurosci 26:3509–3517

    PubMed  Google Scholar 

  • Thierry AM, Gioanni Y, Degenetais E, Glowinski J (2000) Hippocampo-prefrontal cortex pathway: anatomical and electrophysiological characteristics. Hippocampus 10:411–419

    PubMed  CAS  Google Scholar 

  • Tonegawa S, Tsien JZ, McHugh TJ, Huerta P, Blum KI, Wilson MA (1996) Hippocampal CA1-region-restricted knockout of NMDAR1 gene disrupts synaptic plasticity, place fields, and spatial learning. Cold Spring Harb Symp Quant Biol 61:225–238

    PubMed  CAS  Google Scholar 

  • Tsien JZ, Chen DF, Gerber D, Tom C, Mercer EH, Anderson DJ, Mayford M, Kandel ER, Tonegawa S (1996a) Subregion- and cell type-restricted gene knockout in mouse brain. Cell 87:1317–1326

    PubMed  CAS  Google Scholar 

  • Tsien JZ, Huerta PT, Tonegawa S (1996b) The essential role of hippocampal CA1 NMDA receptor-dependent synaptic plasticity in spatial memory. Cell 87:1327–1338

    PubMed  CAS  Google Scholar 

  • Ueda Y, Willmore LJ (2000) Molecular regulation of glutamate and GABA transporter proteins by valproic acid in rat hippocampus during epileptogenesis. Exp Brain Res 133:334–339

    PubMed  CAS  Google Scholar 

  • van Harmelen AL, van Tol MJ, van der Wee NJ, Veltman DJ, Aleman A, Spinhoven P, van Buchem MA, Zitman FG, Penninx BW, Elzinga BM (2010) Reduced Medial Prefrontal Cortex Volume in Adults Reporting Childhood Emotional Maltreatment. Biol Psychiatry 68(9):832–838

    PubMed  Google Scholar 

  • Venero C, Borrell J (1999) Rapid glucocorticoid effects on excitatory amino acid levels in the hippocampus: a microdialysis study in freely moving rats. Eur J Neurosci 11:2465–2473

    PubMed  CAS  Google Scholar 

  • Vyas A, Bernal S, Chattarji S (2003) Effects of chronic stress on dendritic arborization in the central and extended amygdala. Brain Res 965:290–294

    PubMed  CAS  Google Scholar 

  • Vyas A, Mitra R, Shankaranarayana Rao BS, Chattarji S (2002) Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neurons. J Neurosci 22:6810–6818

    PubMed  CAS  Google Scholar 

  • Vyas A, Pillai AG, Chattarji S (2004) Recovery after chronic stress fails to reverse amygdaloid neuronal hypertrophy and enhanced anxiety-like behavior. Neuroscience 128:667–673

    PubMed  CAS  Google Scholar 

  • Walsh T, McClellan JM, McCarthy SE, Addington AM, Pierce SB, Cooper GM, Nord AS, Kusenda M, Malhotra D, Bhandari A, Stray SM, Rippey CF, Roccanova P, Makarov V, Lakshmi B, Findling RL, Sikich L, Stromberg T, Merriman B, Gogtay N, Butler P, Eckstrand K, Noory L, Gochman P, Long R, Chen Z, Davis S, Baker C, Eichler EE, Meltzer PS, Nelson SF, Singleton AB, Lee MK, Rapoport JL, King MC, Sebat J (2008) Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 320:539–543

    PubMed  CAS  Google Scholar 

  • Waltz JA, Gold JM (2007) Probabilistic reversal learning impairments in schizophrenia: further evidence of orbitofrontal dysfunction. Schizophr Res 93:296–303

    PubMed  Google Scholar 

  • Watanabe Y, Gould E, Cameron HA, Daniels DC, McEwen BS (1992a) Phenytoin prevents stress- and corticosterone-induced atrophy of CA3 pyramidal neurons. Hippocampus 2:431–435

    PubMed  CAS  Google Scholar 

  • Watanabe Y, Gould E, McEwen BS (1992b) Stress induces atrophy of apical dendrites of hippocampal CA3 pyramidal neurons. Brain Res 588:341–345

    PubMed  CAS  Google Scholar 

  • Wiedholz LM, Owens WA, Horton RE, Feyder M, Karlsson RM, Hefner K, Sprengel R, Celikel T, Daws LC, Holmes A (2008) Mice lacking the AMPA GluR1 receptor exhibit striatal hyperdopaminergia and ‘schizophrenia-related’ behaviors. Mol Psychiatry 13:631–640

    PubMed  CAS  Google Scholar 

  • Wood GE, Norris EH, Waters E, Stoldt JT, McEwen BS (2008) Chronic immobilization stress alters aspects of emotionality and associative learning in the rat. Behav Neurosci 122:282–292

    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 

  • Yuen EY, Liu W, Karatsoreos IN, Feng J, McEwen BS, Yan Z (2009) Acute stress enhances glutamatergic transmission in prefrontal cortex and facilitates working memory. Proc Natl Acad Sci USA 106:14075–14079

    PubMed  CAS  Google Scholar 

  • Zarate CA, Quiroz J, Payne J, Manji HK (2002) Modulators of the glutamatergic system: implications for the development of improved therapeutics in mood disorders. Psychopharmacol Bull 36:35–83

    PubMed  Google Scholar 

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Graybeal, C., Kiselycznyk, C., Holmes, A. (2011). Stress-Induced Deficits in Cognition and Emotionality: A Role for Glutamate. In: Cryan, J., Reif, A. (eds) Behavioral Neurogenetics. Current Topics in Behavioral Neurosciences, vol 12. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2011_193

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