Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders (original) (raw)
Kessler, R. C. et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch. Gen. Psychiatry62, 593–602 (2005). ArticlePubMed Google Scholar
Fagiolini, A. et al. Functional impairment in the remission phase of bipolar disorder. Bipolar Disord.7, 281–285 (2005). PubMed Google Scholar
Huxley, N. & Baldessarini, R. J. Disability and its treatment in bipolar disorder patients. Bipolar Disord.9, 183–196 (2007). PubMed Google Scholar
Tohen, M. et al. The McLean-Harvard First-Episode Mania Study: prediction of recovery and first recurrence. Am. J. Psychiatry160, 2099–2107 (2003). PubMed Google Scholar
Murray, C. J. & Lopez, A. D. Evidence-based health policy — lessons from the Global Burden of Disease Study. Science274, 740–743 (1996). CASPubMed Google Scholar
Rush, A. J. et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am. J. Psychiatry163, 1905–1917 (2006). PubMed Google Scholar
Trivedi, M. H. et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am. J. Psychiatry163, 28–40 (2006). PubMed Google Scholar
Judd, L. L. et al. The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch. Gen. Psychiatry59, 530–537 (2002). PubMed Google Scholar
Nierenberg, A. A. et al. Treatment-resistant bipolar depression: a STEP-BD equipoise randomized effectiveness trial of antidepressant augmentation with lamotrigine, inositol, or risperidone. Am. J. Psychiatry163, 210–216 (2006). PubMed Google Scholar
Drevets, W. C. Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders. Curr. Opin. Neurobiol.11, 240–249 (2001). CASPubMed Google Scholar
Dunlop, B. W. & Nemeroff, C. B. The role of dopamine in the pathophysiology of depression. Arch. Gen. Psychiatry64, 327–337 (2007). CASPubMed Google Scholar
Manji, H. K., Drevets, W. C. & Charney, D. S. The cellular neurobiology of depression. Nature Med.7, 541–547 (2001). This article reviews the data demonstrating that severe mood disorders arise from abnormalities in synaptic and neural-plasticity cascades. CASPubMed Google Scholar
Berman, R. M., Krystal, J. H. & Charney, D. S. in Biology of Schizophrenia and Affective Disease (ed. Watson, S. J.) 295–368 (American Psychiatric Press, Washington, D.C., 1996). Google Scholar
Manji, H. K., Moore, G. J., Rajkowska, G. & Chen, G. Neuroplasticity and cellular resilience in mood disorders. Millennium Article. Mol. Psychiatry5, 578–593 (2000). CASPubMed Google Scholar
Payne, J. L., Quiroz, J. A., Zarate, C. A. & Manji, H. K. Timing is everything: does the robust upregulation of noradrenergically regulated plasticity genes underlie the rapid antidepressant effects of sleep deprivation? Biol. Psychiatry52, 921–926 (2002). CASPubMed Google Scholar
Orrego, F. & Villanueva, S. The chemical nature of the main central excitatory transmitter: a critical appraisal based upon release studies and synaptic vesicle localization. Neuroscience56, 539–555 (1993). CASPubMed Google Scholar
Krystal, J. H. et al. NMDA agonists and antagonists as probes of glutamatergic dysfunction and pharmacotherapies in neuropsychiatric disorders. Harv. Rev. Psychiatry7, 125–143 (1999). CASPubMed Google Scholar
Erecinska, M. & Silver, I. A. Metabolism and role of glutamate in mammalian brain. Prog. Neurobiol.35, 245–296 (1990). CASPubMed Google Scholar
Varoqui, H., Schafer, M. K., Zhu, H., Weihe, E. & Erickson, J. D. Identification of the differentiation-associated Na+/PI transporter as a novel vesicular glutamate transporter expressed in a distinct set of glutamatergic synapses. J. Neurosci.22, 142–155 (2002). CASPubMedPubMed Central Google Scholar
Herzog, E. et al. Localization of VGLUT3, the vesicular glutamate transporter type 3, in the rat brain. Neuroscience123, 983–1002 (2004). CASPubMed Google Scholar
Peng, J. et al. Semiquantitative proteomic analysis of rat forebrain postsynaptic density fractions by mass spectrometry. J. Biol. Chem.279, 21003–21011 (2004). CASPubMed Google Scholar
Rothstein, J. D., Jin, L., Dykes-Hoberg, M. & Kuncl, R. W. Chronic inhibition of glutamate uptake produces a model of slow neurotoxicity. Proc. Natl Acad. Sci. USA90, 6591–6595 (1993). CASPubMedPubMed Central Google Scholar
Tanaka, K. et al. Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1. Science276, 1699–1702 (1997). CASPubMed Google Scholar
Pitt, D., Nagelmeier, THAT IS, Wilson, H. C. & Raine, C. S. Glutamate uptake by oligodendrocytes: Implications for excitotoxicity in multiple sclerosis. Neurology61, 1113–1120 (2003). CASPubMed Google Scholar
Parsons, C. G., Danysz, W. & Quack, G. Glutamate in CNS disorders as a target for drug development: an update. Drug News Perspect.11, 523–569 (1998). CASPubMed Google Scholar
Francis, P. T. Glutamatergic systems in Alzheimer's disease. Int. J. Geriatr Psychiatry18, S15–S21 (2003). PubMed Google Scholar
Cortese, B. M. & Phan, K. L. The role of glutamate in anxiety and related disorders. CNS Spectr.10, 820–830 (2005). PubMed Google Scholar
Fan, M. M. & Raymond, L. A. _N_-methyl-D-aspartate (NMDA) receptor function and excitotoxicity in Huntington's disease. Prog. Neurobiol.81, 272–293 (2007). CASPubMed Google Scholar
Kim, J. S., Schmid-Burgk, W., Claus, D. & Kornhuber, H. H. Increased serum glutamate in depressed patients. Arch. Psychiatr. Nervenkr.232, 299–304 (1982). CASPubMed Google Scholar
Altamura, C. A. et al. Plasma and platelet excitatory amino acids in psychiatric disorders. Am. J. Psychiatry150, 1731–1733 (1993). CASPubMed Google Scholar
Mauri, M. C. et al. Plasma and platelet amino acid concentrations in patients affected by major depression and under fluvoxamine treatment. Neuropsychobiology37, 124–129 (1998). CASPubMed Google Scholar
Mitani, H. et al. Correlation between plasma levels of glutamate, alanine and serine with severity of depression. Prog. Neuropsychopharmacol. Biol. Psychiatry30, 1155–1158 (2006). CASPubMed Google Scholar
Levine, J. et al. Increased cerebrospinal fluid glutamine levels in depressed patients. Biol. Psychiatry47, 586–593 (2000). CASPubMed Google Scholar
Frye, M. A., Tsai, G. E., Huggins, T., Coyle, J. T. & Post, R. M. Low cerebrospinal fluid glutamate and glycine in refractory affective disorder. Biol. Psychiatry61, 162–166 (2006). PubMed Google Scholar
Francis, P. T. et al. Brain amino acid concentrations and Ca2+-dependent release in intractable depression assessed antemortem. Brain Res.494, 315–324 (1989). CASPubMed Google Scholar
Altamura, C., Maes, M., Dai, J. & Meltzer, H. Y. Plasma concentrations of excitatory amino acids, serine, glycine, taurine and histidine in major depression. Eur. Neuropsychopharmacol.5, 71–75 (1995). CASPubMed Google Scholar
Maes, M., Verkerk, R., Vandoolaeghe, E., Lin, A. & Scharpe, S. Serum levels of excitatory amino acids, serine, glycine, histidine, threonine, taurine, alanine and arginine in treatment-resistant depression: modulation by treatment with antidepressants and prediction of clinical responsivity. Acta Psychiatr. Scand.97, 302–308 (1998). CASPubMed Google Scholar
Hashimoto, K., Sawa, A. & Iyo, M. Increased levels of glutamate in brains from patients with mood disorders. Biol. Psychiatry62, 1310–1316 (2007). CASPubMed Google Scholar
de Graaf, R. A., Mason, G. F., Patel, A. B., Behar, K. L. & Rothman, D. L. _In vivo_1H-[13C]-NMR spectroscopy of cerebral metabolism. NMR Biomed.16, 339–357 (2003). CASPubMed Google Scholar
Nowak, G., Ordway, G. A. & Paul, I. A. Alterations in the _N_-methyl-D-aspartate (NMDA) receptor complex in the frontal cortex of suicide victims. Brain Res.675, 157–164 (1995). CASPubMed Google Scholar
Scarr, E., Pavey, G., Sundram, S., MacKinnon, A. & Dean, B. Decreased hippocampal NMDA, but not kainate or AMPA receptors in bipolar disorder. Bipolar Disord.5, 257–264 (2003). CASPubMed Google Scholar
McCullumsmith, R. E. et al. Decreased NR1, NR2A, and SAP102 transcript expression in the hippocampus in bipolar disorder. Brain Res.1127, 108–118 (2007). In this article, the authors describe alterations in NMDA receptor complex in post-mortem brain tissue of patients with BPD. CASPubMed Google Scholar
Law, A. J. & Deakin, J. F. Asymmetrical reductions of hippocampal NMDAR1 glutamate receptor mRNA in the psychoses. Neuroreport12, 2971–2974 (2001). CASPubMed Google Scholar
Nudmamud-Thanoi, S. & Reynolds, G. P. The NR1 subunit of the glutamate/NMDA receptor in the superior temporal cortex in schizophrenia and affective disorders. Neurosci. Lett.372, 173–177 (2004). CASPubMed Google Scholar
Mundo, E. et al. Evidence that the _N_-methyl-D-aspartate subunit 1 receptor gene (GRIN1) confers susceptibility to bipolar disorder. Mol. Psychiatry8, 241–245 (2003). CASPubMed Google Scholar
Martucci, L. et al. _N_-methyl-D-aspartate receptor NR2B subunit gene GRIN2B in schizophrenia and bipolar disorder: polymorphisms and mRNA levels. Schizophr. Res.84, 214–221 (2006). PubMed Google Scholar
Woo, T. U., Walsh, J. P. & Benes, F. M. Density of glutamic acid decarboxylase 67 messenger RNA-containing neurons that express the _N_-methyl-D-aspartate receptor subunit NR2A in the anterior cingulate cortex in schizophrenia and bipolar disorder. Arch. Gen. Psychiatry61, 649–657 (2004). This article shows that there are alterations in neurons that express NMDA NR2A receptor subunits in post-mortem brain tissue of patients with BPD. CASPubMed Google Scholar
Meador-Woodruff, J. H., Hogg, A. J. Jr., & Smith, R. E. Striatal ionotropic glutamate receptor expression in schizophrenia, bipolar disorder, and major depressive disorder. Brain Res. Bull.55, 631–640 (2001). CASPubMed Google Scholar
Beneyto, M. & Meador-Woodruff, J. H. Lamina-specific abnormalities of AMPA receptor trafficking and signaling molecule transcripts in the prefrontal cortex in schizophrenia. Synapse60, 585–598 (2006). CASPubMed Google Scholar
Kristiansen, L. V. & Meador-Woodruff, J. H. Abnormal striatal expression of transcripts encoding NMDA interacting PSD proteins in schizophrenia, bipolar disorder and major depression. Schizophr. Res.78, 87–93 (2005). PubMed Google Scholar
Clinton, S. M. & Meador-Woodruff, J. H. Abnormalities of the NMDA receptor and associated intracellular molecules in the thalamus in schizophrenia and bipolar disorder. Neuropsychopharmacology29, 1353–1362 (2004). CASPubMed Google Scholar
Toro, C. & Deakin, J. F. NMDA receptor subunit NRI and postsynaptic protein PSD-95 in hippocampus and orbitofrontal cortex in schizophrenia and mood disorder. Schizophr. Res.80, 323–330 (2005). PubMed Google Scholar
Hamidi, M., Drevets, W. C. & Price, J. L. Glial reduction in amygdala in major depressive disorder is due to oligodendrocytes. Biol. Psychiatry55, 563–569 (2004). PubMed Google Scholar
Rajkowska, G. & Miguel-Hidalgo, J. J. Gliogenesis and glial pathology in depression. CNS Neurol. Disord. Drug Targets.6, 219–233 (2007). CASPubMedPubMed Central Google Scholar
Ongur, D., Drevets, W. C. & Price, J. L. Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc. Natl Acad. Sci. USA95, 13290–13295 (1998). This article demonstrates that there is a reduction in the number of frontal cortex glia cells in mood disorders. CASPubMedPubMed Central Google Scholar
Rajkowska, G. et al. Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biol. Psychiatry45, 1085–1098 (1999). CASPubMed Google Scholar
Miguel-Hidalgo, J. J. et al. Glial fibrillary acidic protein immunoreactivity in the prefrontal cortex distinguishes younger from older adults in major depressive disorder. Biol. Psychiatry48, 861–873 (2000). CASPubMed Google Scholar
Rajkowska, G. Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells. Biol. Psychiatry48, 766–777 (2000). CASPubMed Google Scholar
Cotter, D., Mackay, D., Landau, S., Kerwin, R. & Everall, I. Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder. Arch. Gen. Psychiatry58, 545–553 (2001). CASPubMed Google Scholar
Rajkowska, G., Halaris, A. & Selemon, L. D. Reductions in neuronal and glial density characterize the dorsolateral prefrontal cortex in bipolar disorder. Biol. Psychiatry49, 741–752 (2001). CASPubMed Google Scholar
Webster, M. J. et al. Immunohistochemical localization of phosphorylated glial fibrillary acidic protein in the prefrontal cortex and hippocampus from patients with schizophrenia, bipolar disorder, and depression. Brain Behav. Immunity15, 388–400 (2001). CAS Google Scholar
Bowley, M. P., Drevets, W. C., Ongur, D. & Price, J. L. Low glial numbers in the amygdala in major depressive disorder. Biol. Psychiatry52, 404–412 (2002). PubMed Google Scholar
Choudary, P. V. et al. Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression. Proc. Natl Acad. Sci. USA102, 15653–15658 (2005). A microarray study showing that there are alterations in glutamatergic and GABAergic systems in depression. CASPubMedPubMed Central Google Scholar
McCullumsmith, R. E. & Meador-Woodruff, J. H. Striatal excitatory amino acid transporter transcript expression in schizophrenia, bipolar disorder, and major depressive disorder. Neuropsychopharmacology26, 368–375 (2002). CASPubMed Google Scholar
Zarate, C. A., Quiroz, J., Payne, J. & Manji, H. K. Modulators of the glutamatergic system: implications for the development of improved therapeutics in mood disorders. Psychopharmacol. Bull.36, 35–83 (2002). PubMed Google Scholar
Kugaya, A. & Sanacora, G. Beyond monoamines: glutamatergic function in mood disorders. CNS Spectr.10, 808–819 (2005). PubMed Google Scholar
Toro, C. T., Hallak, J. E., Dunham, J. S. & Deakin, J. F. Glial fibrillary acidic protein and glutamine synthetase in subregions of prefrontal cortex in schizophrenia and mood disorder. Neurosci. Lett.404, 276–281 (2006). CASPubMed Google Scholar
Trullas, R. & Skolnick, P. Functional antagonists at the NMDA receptor complex exhibit antidepressant actions. Eur. J. Pharmacol.185, 1–10 (1990). This article discusses the antidepressant-like activity of NMDA antagonists in preclinical models. CASPubMed Google Scholar
Sernagor, E., Kuhn, D., Vyklicky, L. Jr., & Mayer, M. L. Open channel block of NMDA receptor responses evoked by tricyclic antidepressants. Neuron2, 1221–1227 (1989). CASPubMed Google Scholar
Pittaluga, A. et al. Antidepressant treatments and function of glutamate ionotropic receptors mediating amine release in hippocampus. Neuropharmacology53, 27–36 (2007). CASPubMed Google Scholar
Nowak, G., Trullas, R., Layer, R. T., Skolnick, P. & Paul, I. A. Adaptive changes in the _N_-methyl-D-aspartate receptor complex after chronic treatment with imipramine and 1-aminocyclopropanecarboxylic acid. J. Pharmacol. Exp. Ther.265, 1380–1386 (1993). CASPubMed Google Scholar
Paul, I. A., Layer, R. T., Skolnick, P. & Nowak, G. Adaptation of the NMDA receptor in rat cortex following chronic electroconvulsive shock or imipramine. Eur. J. Pharmacol.247, 305–311 (1993). CASPubMed Google Scholar
Paul, I. A., Nowak, G., Layer, R. T., Popik, P. & Skolnick, P. Adaptation of the _N_-methyl-D-aspartate receptor complex following chronic antidepressant treatments. J. Pharmacol. Exp. Ther.269, 95–102 (1994). CASPubMed Google Scholar
Skolnick, P. et al. Adaptation of _N_-methyl-D-aspartate (NMDA) receptors following antidepressant treatment: implications for the pharmacotherapy of depression. Pharmacopsychiatry29, 23–26 (1996). CASPubMed Google Scholar
Nowak, G., Legutko, B., Skolnick, P. & Popik, P. Adaptation of cortical NMDA receptors by chronic treatment with specific serotonin reuptake inhibitors. Eur. J. Pharmacol.342, 367–370 (1998). CASPubMed Google Scholar
Wong, M. L. et al. Differential effects of kindled and electrically induced seizures on a glutamate receptor (GluR1) gene expression. Epilepsy Res.14, 221–227 (1993). CASPubMed Google Scholar
Naylor, P., Stewart, C. A., Wright, S. R., Pearson, R. C. & Reid, I. C. Repeated ECS induces GluR1 mRNA but not NMDAR1A-G mRNA in the rat hippocampus. Mol. Brain Res.35, 349–353 (1996). CASPubMed Google Scholar
Svenningsson, P. et al. Involvement of striatal and extrastriatal DARPP-32 in biochemical and behavioral effects of fluoxetine (Prozac). Proc. Natl Acad. Sci. USA99, 3182–3187 (2002). CASPubMedPubMed Central Google Scholar
Martinez-Turrillas, R., Del Rio, J. & Frechilla, D. Neuronal proteins involved in synaptic targeting of AMPA receptors in rat hippocampus by antidepressant drugs. Biochem. Biophys. Res. Commun.353, 750–755 (2007). CASPubMed Google Scholar
Barbon, A. et al. Regulation of editing and expression of glutamate α-amino-propionic-acid (AMPA)/kainate receptors by antidepressant drugs. Biol. Psychiatry59, 713–720 (2006). CASPubMed Google Scholar
Zarate, C. A. Jr, et al. Regulation of cellular plasticity cascades in the pathophysiology and treatment of mood disorders: role of the glutamatergic system. Ann. NY Acad. Sci.1003, 273–291 (2003). CASPubMed Google Scholar
Bowden, C. L. et al. A randomized, placebo-controlled 12-month trial of divalproex and lithium in treatment of outpatients with bipolar I disorder. Divalproex Maintenance Study Group. Arch. Gen. Psychiatry57, 481–489 (2000). CASPubMed Google Scholar
Hokin, L. E., Dixon, J. F. & Los, G. V. A novel action of lithium: stimulation of glutamate release and inositol 1,4,5 trisphosphate accumulation via activation of the _N_-methyl D-aspartate receptor in monkey and mouse cerebral cortex slices. Adv. Enzyme Regul.36, 229–244 (1996). CASPubMed Google Scholar
Nonaka, S., Hough, C. J. & Chuang, D. M. Chronic lithium treatment robustly protects neurons in the central nervous system against excitotoxicity by inhibiting _N_-methyl-D-aspartate receptor-mediated calcium influx. Proc. Natl Acad. Sci. USA95, 2642–2647 (1998). CASPubMedPubMed Central Google Scholar
Hashimoto, R., Hough, C., Nakazawa, T., Yamamoto, T. & Chuang, D. M. Lithium protection against glutamate excitotoxicity in rat cerebral cortical neurons: involvement of NMDA receptor inhibition possibly by decreasing NR2B tyrosine phosphorylation. J. Neurochem.80, 589–597 (2002). CASPubMed Google Scholar
Du, J. et al. Structurally dissimilar antimanic agents modulate synaptic plasticity by regulating AMPA glutamate receptor subunit GluR1 synaptic expression. Ann. NY Acad. Sci.1003, 378–380 (2003). CASPubMed Google Scholar
Du, J. et al. The role of hippocampal GluR1 and GluR2 receptors in manic-like behaviors. J. Neurosci.28, 68–79 (2008). CASPubMedPubMed Central Google Scholar
Ahmad, S., Fowler, L. J. & Whitton, P. S. Effects of combined lamotrigine and valproate on basal and stimulated extracellular amino acids and monoamines in the hippocampus of freely moving rats. Naunyn Schmiedebergs Arch. Pharmacol.371, 1–8 (2005). CASPubMed Google Scholar
Du, J. et al. The anticonvulsants lamotrigine, riluzole, and valproate differentially regulate AMPA receptor membrane localization: relationship to clinical effects in mood disorders. Neuropsychopharmacology32, 793–802 (2007). CASPubMed Google Scholar
Mizuta, I. et al. Riluzole stimulates nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor synthesis in cultured mouse astrocytes. Neurosci. Lett.310, 117–120 (2001). CASPubMed Google Scholar
Frizzo, M. E., Dall'Onder, L. P., Dalcin, K. B. & Souza, D. O. Riluzole enhances glutamate uptake in rat astrocyte cultures. Cell. Mol. Neurobiol.24, 123–128 (2004). CASPubMed Google Scholar
Debono, M. W., Le Guern, J., Canton, T., Doble, A. & Pradier, L. Inhibition by riluzole of electrophysiological responses mediated by rat kainate and NMDA receptors expressed in Xenopus oocytes. Eur. J. Pharmacol.235, 283–289 (1993). CASPubMed Google Scholar
Jehle, T. et al. Effects of riluzole on electrically evoked neurotransmitter release. Br. J. Pharmacol.130, 1227–1234 (2000). CASPubMedPubMed Central Google Scholar
Zarate, C. A. Jr, et al. An open-label trial of riluzole in patients with treatment-resistant major depression. Am. J. Psychiatry161, 171–174 (2004). PubMed Google Scholar
Zarate, C. A. Jr, et al. An open-label trial of the glutamate-modulating agent riluzole in combination with lithium for the treatment of bipolar depression. Biol. Psychiatry57, 430–432 (2005). CASPubMed Google Scholar
Sanacora, G. et al. Preliminary evidence of riluzole efficacy in antidepressant-treated patients with residual depressive symptoms. Biol. Psychiatry61, 822–825 (2007). CASPubMed Google Scholar
Crane, G. Cycloserine as an antidepressant agent. Am. J. Psychiatry115, 1025–1026 (1959). CASPubMed Google Scholar
Crane, G. The psychotropic effect of cycloserine: a new use of an antibiotic. Comp. Psychiatry2, 51–59 (1961). Google Scholar
Heresco-Levy, U. et al. Controlled trial of D-cycloserine adjuvant therapy for treatment-resistant major depressive disorder. J. Affect Disord.93, 239–243 (2006). CAS Google Scholar
van Berckel, B. N. et al. The partial NMDA agonist D-cycloserine stimulates LH secretion in healthy volunteers. Psychopharmacology (Berl.)138, 190–197 (1998). CAS Google Scholar
van Berckel, B. N. et al. Behavioral and neuroendocrine effects of the partial NMDA agonist D-cycloserine in healthy subjects. Neuropsychopharmacology16, 317–324 (1997). CASPubMed Google Scholar
Davis, M., Ressler, K., Rothbaum, B. O. & Richardson, R. Effects of D-cycloserine on extinction: translation from preclinical to clinical work. Biol. Psychiatry60, 369–375 (2006). CASPubMed Google Scholar
Ressler, K. J. et al. Cognitive enhancers as adjuncts to psychotherapy: use of D-cycloserine in phobic individuals to facilitate extinction of fear. Arch. Gen. Psychiatry61, 1136–1144 (2004). PubMed Google Scholar
Guastella, A. J. et al. A randomized controlled trial of D-cycloserine enhancement of exposure therapy for social anxiety disorder. Biol. Psychiatry63, 544–549 (2008). CASPubMed Google Scholar
Kushner, M. G. et al. D-Cycloserine augmented exposure therapy for obsessive-compulsive disorder. Biol. Psychiatry62, 835–838 (2007). CASPubMed Google Scholar
Reisberg, B. et al. A 24-week open-label extension study of memantine in moderate to severe Alzheimer disease. Arch. Neurol.63, 49–54 (2006). PubMed Google Scholar
Reisberg, B. et al. Memantine in moderate-to-severe Alzheimer's disease. N. Engl. J. Med.348, 1333–1341 (2003). CASPubMed Google Scholar
Teng, C. T. & Demetrio, F. N. Memantine may acutely improve cognition and have a mood stabilizing effect in treatment-resistant bipolar disorder. Rev. Bras. Psiquiatr.28, 252–254 (2006). PubMed Google Scholar
Zarate, C. A. Jr, et al. A randomized trial of an _N_-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch. Gen. Psychiatry63, 856–864 (2006). In this randomized, placebo-controlled, double-blind crossover study, ketamine, an NMDA receptor antagonist, was found to have long-lasting and sustained antidepressant effects that began minutes after its administration. CASPubMed Google Scholar
Ferguson, J. M. & Shingleton, R. N. An open-label, flexible-dose study of memantine in major depressive disorder. Clin. Neuropharmacol.30, 136–144 (2007). CASPubMed Google Scholar
Harrison, N. L. & Simmonds, M. A. Quantitative studies on some antagonists of _N_-methyl D-aspartate in slices of rat cerebral cortex. Br. J. Pharmacol.84, 381–391 (1985). CASPubMedPubMed Central Google Scholar
Zarate, C. A., Charney, D. S. & Manji, H. K. Searching for rational anti-_N_-methyl-D-aspartate treatment for depression. Arch. Gen. Psychiatry64, 1100–1101 (2007). Google Scholar
Moghaddam, B., Adams, B., Verma, A. & Daly, D. Activation of glutamatergic neurotransmission by ketamine: a novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex. J. Neurosci.17, 2921–2927 (1997). CASPubMedPubMed Central Google Scholar
Maeng, S. et al. Cellular mechanisms underlying the antidepressant effects of ketamine: role of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biol. Psychiatry63, 349–352 (2008). CASPubMed Google Scholar
Green, S. M. et al. Intravenous ketamine for pediatric sedation in the emergency department: safety profile with 156 cases. Acad. Emerg. Med.5, 971–976 (1998). CASPubMed Google Scholar
Britt, G. C. & McCance-Katz, E. F. A brief overview of the clinical pharmacology of “club drugs”. Subst. Use Misuse40, 1189–1201 (2005). PubMed Google Scholar
Perry, E. B. Jr, et al. Psychiatric safety of ketamine in psychopharmacology research. Psychopharmacology (Berl.)192, 253–260 (2007). CAS Google Scholar
Carpenter, W. T. J. The schizophrenia ketamine challenge study debate. Biol. Psychiatry46, 1081–1091 (1999). PubMed Google Scholar
Berman, R. M. et al. Antidepressant effects of ketamine in depressed patients. Biol. Psychiatry47, 351–354 (2000). CASPubMed Google Scholar
Bleakman, D. & Lodge, D. Neuropharmacology of AMPA and kainate receptors. Neuropharmacology37, 1187–1204 (1998). CASPubMed Google Scholar
Borges, K. & Dingledine, R. AMPA receptors: molecular and functional diversity. Prog. Brain Res.116, 153–170 (1998). CASPubMed Google Scholar
Black, M. D. Therapeutic potential of positive AMPA modulators and their relationship to AMPA receptor subunits. A review of preclinical data. Psychopharmacology (Berl.)179, 154–163 (2005). CAS Google Scholar
Knapp, R. J. et al. Antidepressant activity of memory-enhancing drugs in the reduction of submissive behavior model. Eur. J. Pharmacol.440, 27–35 (2002). CASPubMed Google Scholar
Li, X. et al. Antidepressant-like actions of an AMPA receptor potentiator (LY392098). Neuropharmacology40, 1028–1033 (2001). CASPubMed Google Scholar
Bai, F., Bergeron, M. & Nelson, D. L. Chronic AMPA receptor potentiator (LY451646) treatment increases cell proliferation in adult rat hippocampus. Neuropharmacology44, 1013–1021 (2003). CASPubMed Google Scholar
Lauterborn, J., Lynch, G., Vanderklish, P., Arai, A. & CM., G. Positive modulation of AMPA receptors increases neurotrophin expression by hippocampal and cortical neurons. J. Neurosci.20, 8–21 (2000). CASPubMedPubMed Central Google Scholar
Lauterborn, J. et al. Chronic elevation of brain-derived neurotrophic factor by ampakines. J. Pharmacol. Exp. Ther.307, 297–305 (2003). CASPubMed Google Scholar
Suetake-Koga, S. et al. In vitro and antinociceptive profile of HON0001, an orally active NMDA receptor NR2B subunit antagonist. Pharmacol. Biochem. Behav.84, 134–141 (2006). CASPubMed Google Scholar
Borza, I. et al. Selective NR1/2B _N_-methyl-D-aspartate receptor antagonists among indole-2-carboxamides and benzimidazole-2-carboxamides. J. Med. Chem.50, 901–914 (2007). CASPubMed Google Scholar
Liverton, N. J. et al. Identification and characterization of 4-methylbenzyl 4-[(pyrimidin-2-ylamino)methyl]piperidine-1-carboxylate, an orally bioavailable, brain penetrant NR2B selective _N_-methyl-D-aspartate receptor antagonist. J. Med. Chem.50, 807–819 (2007). CASPubMed Google Scholar
Preskorn, S. et al. A placebo-controlled trial of the NR2B subunit specific NMDA antagonist CP-101,606 plus paroxetine for treatment resistant depression (TRD). Annual Conference of the American Psychological Association (San Francisco, California) 154 (2007). Google Scholar
Brown, R. H.,Jr. Amyotrophic lateral sclerosis — a new role for old drugs. N. Engl. J. Med.352, 1376–1378 (2005). CASPubMed Google Scholar
Miller, T. M. & Cleveland, D. W. Medicine. Treating neurodegenerative diseases with antibiotics. Science307, 361–362 (2005). CASPubMed Google Scholar
Rothstein, J. D. et al. β-Lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Nature433, 73–77 (2005). CASPubMed Google Scholar
Mineur, Y. S., Picciotto, M. R. & Sanacora, G. Antidepressant-like effects of ceftriaxone in male C57BL/6J mice. Biol. Psychiatry61, 250–252 (2006). PubMed Google Scholar
D'Ascenzo, M. et al. mGluR5 stimulates gliotransmission in the nucleus accumbens. Proc. Natl Acad. Sci. USA104, 1995–2000 (2007). CASPubMedPubMed Central Google Scholar
Haydon, P. G. & Carmignoto, G. Astrocyte control of synaptic transmission and neurovascular coupling. Physiol. Rev.86, 1009–1031 (2006). CASPubMed Google Scholar
Lee, Y., Gaskins, D., Anand, A. & Shekhar, A. Glia mechanisms in mood regulation: a novel model of mood disorders. Psychopharmacology (Berl.)191, 55–65 (2007). Google Scholar
Palucha, A. & Pilc, A. Metabotropic glutamate receptor ligands as possible anxiolytic and antidepressant drugs. Pharmacol. Ther.115, 116–147 (2007). CASPubMed Google Scholar
Witkin, J. M., Marek, G. J., Johnson, B. G. & Schoepp, D. D. Metabotropic glutamate receptors in the control of mood disorders. CNS Neurol. Disord. Drug Targets.6, 87–100 (2007). CASPubMed Google Scholar
Karasawa, J., Shimazaki, T., Kawashima, N. & Chaki, S. AMPA receptor stimulation mediates the antidepressant-like effect of a group II metabotropic glutamate receptor antagonist. Brain Res.1042, 92–98 (2005). CASPubMed Google Scholar
Patil, S. T. et al. Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial. Nature Med.13, 1102–1107 (2007). CASPubMed Google Scholar
Dunayevich, E. et al. Efficacy and tolerability of an mGlu2/3 agonist in the treatment of generalized anxiety disorder. Neuropsychopharmacology 22 Aug 2007 (doi:10.1038/sj.npp.1301531). PubMed Google Scholar
Bonanno, G. et al. Chronic antidepressants reduce depolarization-evoked glutamate release and protein interactions favoring formation of SNARE complex in hippocampus. J. Neurosci.25, 3270–3279 (2005). CASPubMedPubMed Central Google Scholar
Wang, M., Yang, Y., Dong, Z., Cao, J. & Xu, L. NR2B-containing _N_-methyl-D-aspartate subtype glutamate receptors regulate the acute stress effect on hippocampal long-term potentiation/long-term depression in vivo. Neuroreport17, 1343–1346 (2006). CASPubMed Google Scholar
Lesch, K. P. & Schmitt, A. Antidepressants and gene expression profiling: how to SNARE novel drug targets. Pharmacogenomics J.2, 346–348 (2002). CASPubMed Google Scholar
Thompson, C. M. et al. Inhibitor of the glutamate vesicular transporter (VGLUT). Curr. Med. Chem.12, 2041–2056 (2005). CASPubMed Google Scholar
Baker, D. A., Xi, Z. X., Shen, H., Swanson, C. J. & Kalivas, P. W. The origin and neuronal function of in vivo nonsynaptic glutamate. J. Neurosci.22, 9134–9141 (2002). CASPubMedPubMed Central Google Scholar
Moran, M. M., McFarland, K., Melendez, R. I., Kalivas, P. W. & Seamans, J. K. Cystine/glutamate exchange regulates metabotropic glutamate receptor presynaptic inhibition of excitatory transmission and vulnerability to cocaine seeking. J. Neurosci.25, 6389–6393 (2005). CASPubMedPubMed Central Google Scholar
Lafleur, D. L. et al. _N_-acetylcysteine augmentation in serotonin reuptake inhibitor refractory obsessive-compulsive disorder. Psychopharmacology (Berl.)184, 254–256 (2006). CAS Google Scholar
LaRowe, S. D. et al. Is cocaine desire reduced by _N_-acetylcysteine? Am. J. Psychiatry164, 1115–1117 (2007). PubMed Google Scholar
Carlson, P. J., Singh, J. B., Zarate, C. A. Jr, Drevets, W. C. & Manji, H. K. Neural circuitry and neuroplasticity in mood disorders: insights for novel therapeutic targets. NeuroRx3, 22–41 (2006). CASPubMedPubMed Central Google Scholar
Du, J. et al. Modulation of synaptic plasticity by antimanic agents: the role of AMPA glutamate receptor subunit 1 synaptic expression. J. Neurosci.24, 6578–6589 (2004). CASPubMedPubMed Central Google Scholar
Conn, P. J. Physiological roles and therapeutic potential of metabotropic glutamate receptors. Ann. NY Acad. Sci.1003, 12–21 (2003). CASPubMed Google Scholar
Balazs, R., Bridges, R. J. & Cotman, C. W. Excitatory Amino Acid Transmission in Health and Disease (Oxford University Press, USA, New York, 2005). Google Scholar
Hardingham, G. E., Fukunaga, Y. & Bading, H. Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways. Nature Neurosci.5, 405–414 (2002). CASPubMed Google Scholar
Ivanov, A. et al. Opposing role of synaptic and extrasynaptic NMDA receptors in regulation of the extracellular signal-regulated kinases (ERK) activity in cultured rat hippocampal neurons. J. Physiol.572, 789–798 (2006). CASPubMedPubMed Central Google Scholar
Agid, Y. et al. How can drug discovery for psychiatric disorders be improved? Nature Rev. Drug Discov.6, 189–201 (2007). CAS Google Scholar
Michael-Titus, A. T., Bains, S., Jeetle, J. & Whelpton, R. Imipramine and phenelzine decrease glutamate overflow in the prefrontal cortex — a possible mechanism of neuroprotection in major depression? Neuroscience100, 681–684 (2000). CASPubMed Google Scholar
White, G., Lovinger, D. M., Peoples, R. W. & Weight, F. F. Inhibition of _N_-methyl-D-aspartate activated ion current by desmethylimipramine. Brain Res.537, 337–339 (1990). CASPubMed Google Scholar
Boyer, P. A., Skolnick, P. & Fossom, L. H. Chronic administration of imipramine and citalopram alters the expression of NMDA receptor subunit mRNAs in mouse brain. A quantitative in situ hybridization study. J. Mol. Neurosci.10, 219–233 (1998). CASPubMed Google Scholar
Song, I. et al. Interaction of the _N_-ethylmaleimide-sensitive factor with AMPA receptors. Neuron21, 393–400 (1998). CASPubMed Google Scholar
Stoll, L., Seguin, S. & Gentile, L. Tricyclic antidepressants, but not the selective serotonin reuptake inhibitor fluoxetine, bind to the S1S2 domain of AMPA receptors. Arch. Biochem. Biophys.458, 213–219 (2007). CASPubMed Google Scholar
Moutsimilli, L. et al. Selective cortical VGLUT1 increase as a marker for antidepressant activity. Neuropharmacology49, 890–900 (2005). CASPubMed Google Scholar
Tordera, R. M., Pei, Q. & Sharp, T. Evidence for increased expression of the vesicular glutamate transporter, VGLUT1, by a course of antidepressant treatment. J. Neurochem.94, 875–883 (2005). CASPubMed Google Scholar
Dixon, J. F., Los, G. V. & Hokin, L. E. Lithium stimulates glutamate “release” and inositol 1,4,5-trisphosphate accumulation via activation of the _N_-methyl-D-aspartate receptor in monkey and mouse cerebral cortex slices. Proc. Natl Acad. Sci. USA91, 8358–8362 (1994). CASPubMedPubMed Central Google Scholar
Dixon, J. F. & Hokin, L. E. Lithium stimulates accumulation of second-messenger inositol 1,4,5-trisphosphate and other inositol phosphates in mouse pancreatic minilobules without inositol supplementation. Biochem. J.304, 251–258 (1994). CASPubMedPubMed Central Google Scholar
Ma, J. & Zhang, G. Y. Lithium reduced _N_-methyl-D-aspartate receptor subunit 2A tyrosine phosphorylation and its interactions with Src and Fyn mediated by PSD-95 in rat hippocampus following cerebral ischemia. Neurosci. Lett.348, 185–189 (2003). CASPubMed Google Scholar
Karkanias, N. B. & Papke, R. L. Lithium modulates desensitization of the glutamate receptor subtype gluR3 in Xenopus oocytes. Neurosci. Lett.277, 153–156 (1999). CASPubMed Google Scholar
Kang, T. C. et al. Valproic acid reduces enhanced vesicular glutamate transporter immunoreactivities in the dentate gyrus of the seizure prone gerbil. Neuropharmacology49, 912–921 (2005). CASPubMed Google Scholar
Cunningham, M. O., Woodhall, G. L. & Jones, R. S. Valproate modifies spontaneous excitation and inhibition at cortical synapses in vitro. Neuropharmacology45, 907–917 (2003). CASPubMed Google Scholar
Ueda, Y. & Willmore, L. J. Molecular regulation of glutamate and GABA transporter proteins by valproic acid in rat hippocampus during epileptogenesis. Exp. Brain Res.133, 334–339 (2000). CASPubMed Google Scholar
Hassel, B., Iversen, E. G., Gjerstad, L. & Tauboll, E. Up-regulation of hippocampal glutamate transport during chronic treatment with sodium valproate. J. Neurochem.77, 1285–1292 (2001). CAS Google Scholar
Loscher, W. Effects of the antiepileptic drug valproate on metabolism and function of inhibitory and excitatory amino acids in the brain. Neurochem. Res.18, 485–502 (1993). CASPubMed Google Scholar
Zeise, M. L., Kasparow, S. & Zieglgansberger, W. Valproate suppresses _N_-methyl-D-aspartate-evoked, transient depolarizations in the rat neocortex in vitro. Brain Res.544, 345–348 (1991). CASPubMed Google Scholar
Ko, G. Y., Brown-Croyts, L. M. & Teyler, T. J. The effects of anticonvulsant drugs on NMDA-EPSP, AMPA-EPSP, and GABA-IPSP in the rat hippocampus. Brain Res. Bull.42, 297–302 (1997). CASPubMed Google Scholar
Turski, L. The _N_-methyl-D-aspartate receptor complex. Various sites of regulation and clinical consequences. Arzneimittelforschung40, 511–514 (1990) (in German). CASPubMed Google Scholar
Steppuhn, K. G. & Turski, L. Modulation of the seizure threshold for excitatory amino acids in mice by antiepileptic drugs and chemoconvulsants. J. Pharmacol. Exp. Ther.265, 1063–1070 (1993). CASPubMed Google Scholar
Kunig, G. et al. Inhibition of [3H]α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid [AMPA] binding by the anticonvulsant valproate in clinically relevant concentrations: an autoradiographic investigation in human hippocampus. Epilepsy Res.31, 153–157 (1998). CASPubMed Google Scholar
Basselin, M., Chang, L., Bell, J. M. & Rapoport, S. I. Chronic lithium chloride administration attenuates brain NMDA receptor-initiated signaling via arachidonic acid in unanesthetized rats. Neuropsychopharmacology31, 1659–1674 (2006). CASPubMed Google Scholar
Zarate, C. A. J. et al. A double-blind, placebo-controlled study of memantine in the treatment of major depression. Am. J. Psychiatry163, 153–155 (2006). PubMed Google Scholar