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Glutamate-based Therapies for Psychiatric Disorders pp 1–20Cite as

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N-Methyl-d-Aspartate (NMDA) Antagonists for the Treatment of Depression

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Part of the book series: Milestones in Drug Therapy ((MDT))

Abstract

Depression is a major public health concern that affects ∼5% of the population in industrialized societies in any given year. Drugs that increase the synaptic availability of biogenic amines (norepinephrine, serotonin, and/or dopamine) have been used to treat depression for over five decades. While the most widely used antidepressants (serotonin and/or norepinephrine selective reuptake inhibitors) are generally safe and effective for many individuals, these drugs are far from ideal. For example, controlled clinical studies have repeatedly demonstrated that ≥2–4 weeks of treatment are required to provide palpable symptom relief. In addition, between 30 and 40% of patients do not respond to a first course of therapy with these biogenic amine-based agents. By contrast, N-methyl-d-aspartate (NMDA) receptor antagonists have been reported to produce rapid and robust antidepressant effects in patients unresponsive to conventional antidepressants. The use of these agents as antidepressants is grounded on a corpus of preclinical evidence, first published 20 years ago, demonstrating the antidepressant-like properties of NMDA antagonists and that chronic treatment with conventional antidepressants attenuates NMDA receptor function. In this chapter, we describe evidence that NMDA antagonists represent an effective alternative to biogenic amine-based agents for treating depression and provide perspective on the hurdles that could impede the development and commercialization of these agents in the face of this remarkable clinical data.

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References

  1. Murray CJ, Lopez AD (1996) Evidence-based health policy–lessons from the Global Burden of Disease Study. Science 274:740–743

    PubMed  CAS  Google Scholar 

  2. American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Association Press, Washington DC

    Google Scholar 

  3. Kendler KS, Eaves LJ, Walters EE, Neale MC, Heath AC, Kessler RC (1996) The identification and validation of distinct depressive syndromes in a population-based sample of female twins. Arch Gen Psychiatry 53:391–399

    PubMed  CAS  Google Scholar 

  4. Kendler KS, Davis CG, Kessler RC (1997) The familial aggregation of common psychiatric and substance use disorders in the National Comorbidity Survey: a family history study. Br J Psychiatry 170:541–548

    PubMed  CAS  Google Scholar 

  5. Berton O, Nestler EJ (2006) New approaches to antidepressant drug discovery: beyond monoamines. Nat Rev Neurosci 7:137–151

    PubMed  CAS  Google Scholar 

  6. Munafo MR, Durrant C, Lewis G, Flint J (2009) Gene X environment interactions at the serotonin transporter locus. Biol Psychiatry 65:211–219

    PubMed  CAS  Google Scholar 

  7. Tsankova NM, Berton O, Renthal W, Kumar A, Neve RL, Nestler EJ (2006) Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat Neurosci 9:519–525

    PubMed  CAS  Google Scholar 

  8. McGowan PO, Sasaki A, D’Alessio AC, Dymov S, Labonte B, Szyf M, Turecki G, Meaney MJ (2009) Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci 12:342–348

    PubMed  CAS  Google Scholar 

  9. Szyf M, Weaver I, Meaney M (2007) Maternal care, the epigenome and phenotypic differences in behavior. Reprod Toxicol 24:9–19

    PubMed  CAS  Google Scholar 

  10. Smith D, Dempster C, Glanville J, Freemantle N, Anderson I (2002) Efficacy and tolerability of venlafaxine compared with selective serotonin reuptake inhibitors and other antidepressants: a meta-analysis. Br J Psychiatry 180:396–404

    PubMed  Google Scholar 

  11. Skolnick P (1999) Antidepressants for the new millenium. Eur J Pharmacol 375:31–40

    PubMed  CAS  Google Scholar 

  12. Rosenzweig-Lipson S, Beyer CE, Hughes ZA, Khawaja X, Rajarao SJ, Malberg JE, Rahman Z, Ring RH, Schechter LE (2007) Differentiating antidepressants of the future: efficacy and safety. Pharmacol Ther 113:134–153

    PubMed  CAS  Google Scholar 

  13. Rush AJ, Trivedi MH, Wisniewski SR, Stewart JW, Nierenberg AA, Thase ME, Ritz L, Biggs MM, Warden D, Luther JF et al (2006) Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med 354:1231–1242

    PubMed  CAS  Google Scholar 

  14. Trullas R, Skolnick P (1990) Functional antagonists at the NMDA receptor complex exhibit antidepressant actions. Eur J Pharmacol 185:1–10

    PubMed  CAS  Google Scholar 

  15. Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH (2000) Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 47:351–354

    PubMed  CAS  Google Scholar 

  16. Price RB, Nock MK, Charney DS, Mathew SJ (2009) Effects of intravenous ketamine on explicit and implicit measures of suicidality in treatment-resistant depression. Biol Psychiatry 66:522–526

    PubMed  CAS  Google Scholar 

  17. Phelps LE, Brutsche N, Moral JR, Luckenbaugh DA, Manji HK, Zarate CA Jr (2009) Family History of alcohol dependence and initial antidepressant response to an N-methyl-d-aspartate antagonist. Biol Psychiatry 65:181–184

    PubMed  CAS  Google Scholar 

  18. Preskorn SH, Baker B, Kolluri S, Menniti FS, Krams M, Landen JW (2008) An innovative design to establish proof of concept of the antidepressant effects of the NR2B subunit selective N-methyl-d-aspartate antagonist, CP-101, 606, in patients with treatment-refractory major depressive disorder. J Clin Psychopharmacol 28:631–637

    PubMed  CAS  Google Scholar 

  19. Shors TJ, Seib TB, Levine S, Thompson RF (1989) Inescapable versus escapable shock modulates long-term potentiation in the rat hippocampus. Science 244:224–226

    PubMed  CAS  Google Scholar 

  20. Harris EW, Ganong AH, Cotman CW (1984) Long-term potentiation in the hippocampus involves activation of N-methyl-d-aspartate receptors. Brain Res 323:132–137

    PubMed  CAS  Google Scholar 

  21. Morris RGM, Anderson E, Lynch G, Baudry M (1986) Selective impairment of learning and blockade of long-term potentiation by N-methyl-d-aspartate receptor antagonist, AP5. Nature 319:774–776

    PubMed  CAS  Google Scholar 

  22. Seligman ME (1978) Learned helplessness as a model of depression. Comment and integration. J Abnorm Psychol 87:165–179

    PubMed  CAS  Google Scholar 

  23. Maier SF, Watkins LR (2005) Stressor controllability and learned helplessness: the roles of the dorsal raphe nucleus, serotonin, and corticotropin-releasing factor. Neurosci Biobehav Rev 29:829–841

    PubMed  CAS  Google Scholar 

  24. Leshner AI, Remler H, Biegon A, Samuel D (1979) Desmethylimipramine (DMI) counteracts learned helplessness in rats. Psychopharmacology 66:207–208

    PubMed  CAS  Google Scholar 

  25. Porsolt RD, Bertin A, Jalfre M (1977) Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Thér 229:327–336

    PubMed  CAS  Google Scholar 

  26. Porsolt RD, Lenegre A (1992) Behavioral models of depression. In: Elliott JM, Heal DJ, Marsden CA (eds) Experimental approaches to anxiety and depression. Wiley, London, pp 73–85

    Google Scholar 

  27. Kos T, Legutko B, Danysz W, Samoriski G, Popik P (2006) Enhancement of antidepressant-like effects but not BDNF mRNA expression by the novel NMDA receptor antagonist neramexane in mice. J Pharmacol Exp Ther 318:1128–1136

    PubMed  CAS  Google Scholar 

  28. Garcia LS, Comim CM, Valvassori SS, Reus GZ, Barbosa LM, Andreazza AC, Stertz L, Fries GR, Gavioli EC, Kapczinski F et al (2008) Acute administration of ketamine induces antidepressant-like effects in the forced swimming test and increases BDNF levels in the rat hippocampus. Prog Neuropsychopharmacol Biol Psychiatry 32:140–144

    PubMed  CAS  Google Scholar 

  29. Maeng S, Zarate CA Jr, Du J, Schloesser RJ, McCammon J, Chen G, Manji HK (2008) Cellular mechanisms underlying the antidepressant effects of ketamine: role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biol Psychiatry 63:349–352

    PubMed  CAS  Google Scholar 

  30. Nowak G, Szewczyk B, Pilc A (2005) Zinc and depression. An update. Pharmacol Rep 57:713–718

    PubMed  CAS  Google Scholar 

  31. Popik P, Kos T, Sowa-Kucma M, Nowak G (2008) Lack of persistent effects of ketamine in rodent models of depression. Psychopharmacology 198:421–430

    PubMed  CAS  Google Scholar 

  32. Paul IA, Skolnick P (2003) Glutamate and depression: clinical and preclinical studies. Ann NY Acad Sci 1003:250–272

    PubMed  CAS  Google Scholar 

  33. Papp M, Moryl E (1993) Similar effect of chronic treatment with imipramine and the NMDA antagonists CGP 37849 and MK-801 in a chronic mild stress model of depression in rats. Eur Neuropsychopharmacol 3:348–349

    Google Scholar 

  34. Papp M, Moryl E (1993) New evidence for the antidepressant activity of MK-801, a non-competitive antagonist of NMDA receptors. Pol J Pharmacol 45:549–553

    PubMed  CAS  Google Scholar 

  35. Papp M, Moryl E (1994) Antidepressant activity of non-competitive NMDA antagonists in a chronic mild stress model of depression. Eur J Pharmacol 263:1–7

    PubMed  CAS  Google Scholar 

  36. Papp M, Moryl E (1996) Antidepressant-like effects of 1-aminocyclopropanecarboxylic acid and D-cycloserine in an animal model of depression. Eur J Pharmacol 316:145–151

    PubMed  CAS  Google Scholar 

  37. Willner P (1997) Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacology (Berl) 134:319–329

    CAS  Google Scholar 

  38. Willner P, Papp M (1997) Animal models to detect antidepressants. Are new strategies necessary to detect new agents? In: Skolnick P (ed) Antidepressants new pharmacological strategies. Humana Press, Totowa, New Jersey, pp 213–230

    Google Scholar 

  39. Meloni D, Gambarana C, De Montis MG, Dal Pra P, Taddei I, Tagliamonte A (1993) Dizocilpine antagonizes the effect of chronic imipramine on learned helplessness in rats. Pharmacol Biochem Behav 46(2):423–426

    PubMed  CAS  Google Scholar 

  40. Kelly JP, Wrynn AS, Leonard BE (1997) The olfactory bulbectomized rat as a model of depression: an update. Pharmacol Ther 74:299–316

    PubMed  CAS  Google Scholar 

  41. Oswald J, Brezinowa V, Dunleavy DLF (1972) On the slowness of action of tricyclic antidepressant drugs. Br J Psychiatry 120:673–677

    PubMed  CAS  Google Scholar 

  42. Manji HK, Drevets WC, Charney DS (2001) The cellular neurobiology of depression. Nat Med 7:541–547

    PubMed  CAS  Google Scholar 

  43. Vetulani J, Sulser F (1975) Action of various antidepressant treatments reduces reactivity of noradrenergic cyclic AMP-generating system in limbic forebrain. Nature 257:495–496

    PubMed  CAS  Google Scholar 

  44. Skolnick P, Legutko B, Li X, Bymaster FP (2001) Current perspectives on the development of non-biogenic amine-based antidepressants. Pharmacol Res 43:411–423

    PubMed  CAS  Google Scholar 

  45. Sanacora G, Zarate CA, Krystal JH, Manji HK (2008) Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nat Rev Drug Discov 7:426–437

    PubMed  CAS  Google Scholar 

  46. Alt A, Nisenbaum ES, Bleakman D, Witkin JM (2006) A role for AMPA receptors in mood disorders. Biochem Pharmacol 71:1273–1288

    PubMed  CAS  Google Scholar 

  47. Skolnick P, Layer RT, Popik P, Nowak G, Paul IA, Trullas R (1996) Adaptation of the N-methyl-d-aspartate (NMDA) receptors following antidepressant treatment: implications for the pharmacotherapy of depression. Pharmacopsychiatry 29:23–26

    PubMed  CAS  Google Scholar 

  48. Paul IA, Layer RT, Skolnick P, Nowak G (1993) Adaptation of the NMDA receptor in rat cortex following chronic electroconvulsive shock or imipramine. Eur J Pharmacol 247:305–311

    PubMed  CAS  Google Scholar 

  49. Paul IA, Nowak G, Layer RT, Popik P, Skolnick P (1994) Adaptation of the N-methyl-d-aspartate receptor complex following chronic antidepressant treatments. J Pharmacol Exp Ther 269:95–102

    PubMed  CAS  Google Scholar 

  50. Nowak G, Trullas R, Layer R, Skolnick P, Paul IA (1993) 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

    PubMed  CAS  Google Scholar 

  51. Nowak G, Legutko B, Skolnick P, Popik P (1998) Adaptation of cortical NMDA receptors by chronic treatment with specific serotonin reuptake inhibitors. Eur J Pharmacol 342:367–370

    PubMed  CAS  Google Scholar 

  52. Nowak G, Li Y, Paul IA (1996) Adaptation of cortical but not hippocampal NMDA receptors after chronic citalopram treatment. Eur J Pharmacol 295:75–85

    PubMed  CAS  Google Scholar 

  53. Kleckner NW, Dingledine R (1988) Requirement for glycine in activation of NMDA receptors expressed in Xenopus oocytes. Science 241:835–837

    PubMed  CAS  Google Scholar 

  54. Boyer PA, Skolnick P, Fossom LH (1998) 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

    PubMed  CAS  Google Scholar 

  55. Popik P, Wrobel M, Nowak G (2000) Chronic treatment with antidepressants affects glycine/NMDA receptor function: behavioral evidence. Neuropharmacology 39:2278–2287

    PubMed  CAS  Google Scholar 

  56. Bobula B, Tokarski K, Hess G (2003) Repeated administration of antidepressants decreases field potentials in rat frontal cortex. Neuroscience 120:765–769

    PubMed  CAS  Google Scholar 

  57. Tokarski K, Bobula B, Wabno J, Hess G (2008) Repeated administration of imipramine attenuates glutamatergic transmission in rat frontal cortex. Neuroscience 153:789–795

    PubMed  CAS  Google Scholar 

  58. Bobula B, Hess G (2008) Antidepressant treatments-induced modifications of glutamatergic transmission in rat frontal cortex. Pharmacol Rep 60:865–871

    PubMed  CAS  Google Scholar 

  59. Trullas R (1997) Functional NMDA antagonists: a new class of antidepressant agents. In: Skolnick P (ed) Antidepressants new pharmacological strategies. Humana Press, Totowa, New Jersey, pp 103–124

    Google Scholar 

  60. Skolnick P, Popik P, Trullas R (2009) Glutamate-based antidepressants: 20 years on. Trends Pharmacol Sci 30:563–569

    PubMed  CAS  Google Scholar 

  61. Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK (2006) A randomized trial of an N-methyl-d-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 63:856–864

    PubMed  CAS  Google Scholar 

  62. Lovinger DM, White G, Weight FF (1989) Ethanol inhibits NMDA-activated ion current in hippocampal neurons. Science 243:1721–1724

    PubMed  CAS  Google Scholar 

  63. Rammes G, Danysz W, Parsons CG (2008) Pharmacodynamics of memantine: an update. Curr Neuropharmacol 6:55–78

    PubMed  CAS  Google Scholar 

  64. Zarate CA Jr, Singh JB, Quiroz JA, De Jesus G, Denicoff KK, Luckenbaugh DA, Manji HK, Charney DS (2006) A double-blind, placebo-controlled study of memantine in the treatment of major depression. Am J Psychiatry 163:153–155

    PubMed  Google Scholar 

  65. Ferguson JM, Shingleton RN (2007) An open-label, flexible-dose study of memantine in major depressive disorder. Clin Neuropharmacol 30:136–144

    PubMed  CAS  Google Scholar 

  66. Fava M, Evins AE, Dorer DJ, Schoenfeld DA (2003) The problem of the placebo response in clinical trials for psychiatric disorders: culprits, possible remedies, and a novel study design approach. Psychother Psychosom 72:115–127

    PubMed  Google Scholar 

  67. Parsons CG, Danysz W, Quack G (1999) Memantine is a clinically well tolerated N-methyl-d-aspartate (NMDA) receptor antagonist – a review of preclinical data. Neuropharmacology 38:735–767

    PubMed  CAS  Google Scholar 

  68. Kotermanski SE, Johnson JW (2009) Mg2+ imparts NMDA receptor subtype selectivity to the Alzheimer’s drug memantine. J Neurosci 29:2774–2779

    PubMed  CAS  Google Scholar 

  69. Kemp JA, McKernan RM (2002) NMDA receptor pathways as drug targets. Nat Neurosci 5:1039–1042, Suppl

    PubMed  CAS  Google Scholar 

  70. Ikonomidou C, Turski L (2002) Traumatic brain injury. In: Lodge D, Danysz W, Parsons CG (eds) Ionotropic glutamate receptors as therapeutic targets. F.P. Graham Publishing Co., Johnson City, TN, pp 447–466, Biomedical Book Series

    Google Scholar 

  71. Loftis JM, Janowsky A (2003) The N-methyl-d-aspartate receptor subunit NR2B: localization, functional properties, regulation, and clinical implications. Pharmacol Ther 97:55–85

    PubMed  CAS  Google Scholar 

  72. Gogas KR (2006) Glutamate-based therapeutic approaches: NR2B receptor antagonists. Curr Opin Pharmacol 6:68–74

    PubMed  CAS  Google Scholar 

  73. Nicholson KL, Mansbach RS, Menniti FS, Balster RL (2007) The phencyclidine-like discriminative stimulus effects and reinforcing properties of the NR2B-selective N-methyl-d-aspartate antagonist CP-101 606 in rats and rhesus monkeys. Behav Pharmacol 18:731–743

    PubMed  CAS  Google Scholar 

  74. Choi DW, Rothman SM (1990) The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death. Annu Rev Neurosci 13:171–182

    PubMed  CAS  Google Scholar 

  75. Albers GW, Goldberg MP, Choi DW (1992) Do NMDA antagonists prevent neuronal injury? Yes. Arch Neurol 49:418–420

    PubMed  CAS  Google Scholar 

  76. O’Neil M, Lees KR (2002) Stroke. In: Lodge D, Danysz W, Parsons CG (eds) Ionotropic glutamate receptors as therapeutic targets. F.P. Graham Publishing Co, Johnson City, TN, pp 403–446, Biomedical Book Series

    Google Scholar 

  77. Muir KW (2006) Glutamate-based therapeutic approaches: clinical trials with NMDA antagonists. Curr Opin Pharmacol 6:53–60

    PubMed  CAS  Google Scholar 

  78. Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT (2008) Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Med 5:e45

    PubMed  Google Scholar 

  79. Leber P (2000) The use of placebo control groups in the assessment of psychiatric drugs: an historical context. Biol Psychiatry 47:699–706

    PubMed  CAS  Google Scholar 

  80. Quitkin FM, Rabkin JG, Gerald J, Davis JM, Klein DF (2000) Validity of clinical trials of antidepressants. Am J Psychiatry 157:327–337

    PubMed  CAS  Google Scholar 

  81. Khan A, Khan SR, Walens G, Kolts R, Giller EL (2003) Frequency of positive studies among fixed and flexible dose antidepressant clinical trials: an analysis of the food and drug administration summary basis of approval reports. Neuropsychopharmacology 28:552–557

    PubMed  CAS  Google Scholar 

  82. Suetake-Koga S, Shimazaki T, Takamori K, Chaki S, Kanuma K, Sekiguchi Y, Suzuki T, Kikuchi T, Matsui Y, Honda T (2006) In vitro and antinociceptive profile of HON0001, an orally active NMDA receptor NR2B subunit antagonist. Pharmacol Biochem Behav 84:134–141

    PubMed  CAS  Google Scholar 

  83. Liverton NJ, Bednar RA, Bednar B, Butcher JW, Claiborne CF, Claremon DA, Cunningham M, DiLella AG, Gaul SL, Libby BE et al (2007) 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

    PubMed  CAS  Google Scholar 

  84. Olney JW, Labruyere J, Price MT (1989) Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs. Science 244:1360–1362

    PubMed  CAS  Google Scholar 

  85. Rogoz Z, Skuza G, Maj J, Danysz W (2002) Synergistic effect of uncompetitive NMDA receptor antagonists and antidepressant drugs in the forced swimming test in rats. Neuropharmacology 42:1024–1030

    PubMed  CAS  Google Scholar 

  86. Gold PW, Chrousos GP (2002) Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states. Mol Psychiatry 7:254–275

    PubMed  CAS  Google Scholar 

  87. Sapolsky RM (1996) Why stress is bad for your brain. Science 273:749–750

    PubMed  CAS  Google Scholar 

  88. Sapolsky RM (2001) Depression, antidepressants, and the shrinking hippocampus. Proc Natl Acad Sci USA 98:12320–12322

    PubMed  CAS  Google Scholar 

  89. McEwen BS (2000) Effects of adverse experiences for brain structure and function. Biol Psychiatry 48:721–731

    PubMed  CAS  Google Scholar 

  90. Zarate CA Jr, Singh J, Manji HK (2006) Cellular plasticity cascades: targets for the development of novel therapeutics for bipolar disorder. Biol Psychiatry 59:1006–1020

    PubMed  CAS  Google Scholar 

  91. 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 

  92. Duman RS, Monteggia LM (2006) A neurotrophic model for stress-related mood disorders. Biol Psychiatry 59:1116–1127

    PubMed  CAS  Google Scholar 

  93. Duman RS, Nibuya M, Vaidya VA (1997) A role for CREB in antidepressant action. In: Skolnick P (ed) Antidepressants new pharmacological strategies. Humana Press, Totowa, New Jersey, pp 173–194

    Google Scholar 

  94. Mamounas LA, Blue ME, Siuciak JA, Altar CA (1995) Brain-derived neurotrophic factor promotes the survival and sprouting of serotonergic axons in rat brain. J Neurosci 15:7929–7939

    PubMed  CAS  Google Scholar 

  95. Tong L, Perez-Polo R (1998) Brain-derived neurotrophic factor (BDNF) protects cultured rat cerebellar granule neurons against glucose deprivation-induced apoptosis. J Neural Transm 105:905–914

    PubMed  CAS  Google Scholar 

  96. Zuccato C, Cattaneo E (2009) Brain-derived neurotrophic factor in neurodegenerative diseases. Nat Rev Neurol 5:311–322

    PubMed  CAS  Google Scholar 

  97. Altar CA (1999) Neurotrophins and depression. Trends Pharmacol Sci 20:59–61

    PubMed  CAS  Google Scholar 

  98. Duman RS, Heninger GR, Nestler EJ (1997) A molecular and cellular theory of depression. Arch Gen Psychiatry 54:597–606

    PubMed  CAS  Google Scholar 

  99. Lodge D et al (2002) Ionotropic glutamate receptors as therapeutic targets. F.P. Graham Publishing Co., Johnson city, TN, Biomedical Book Series

    Google Scholar 

  100. Pliakas AM, Carlson RR, Neve RL, Konradi C, Nestler EJ, Carlezon WA (2001) Altered responsiveness to cocaine and increased immobility in the forced swim test associated with elevated cAMP response element-binding protein expression in nucleus accumbens. J Neurosci 21:7397–7403

    PubMed  CAS  Google Scholar 

  101. Brandoli C, Sanna A, De Bernardi MA, Follesa P, Brooker G, Mocchetti I (1998) Brain-derived neurotrophic factor and basic fibroblast growth factor downregulate NMDA receptor function in cerebellar granule cells. J Neurosci 18:7953–7961

    PubMed  CAS  Google Scholar 

  102. Dybala M, Siwek A, Poleszak E, Pilc A, Nowak G (2008) Lack of NMDA–AMPA interaction in antidepressant-like effect of CGP 37849, an antagonist of NMDA receptor, in the forced swim test. J Neural Transm 115:1519–1520

    PubMed  CAS  Google Scholar 

  103. Stahl SM (2000) Placebo-controlled comparison of the selective serotonin reuptake inhibitors citalopram and sertraline. Biol Psychiatry 48:894–901

    PubMed  CAS  Google Scholar 

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  1. Division of Pharmacotherapies and Medical Consequences of Drug Abuse, National Institute on Drug Abuse, National Institutes of Health, 6001 Executive Blvd, Bethesda, MD, 20892-9551, USA

    Phil Skolnick

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    Phil Skolnick

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Skolnick, P., Popik, P., Trullas, R. (2010). N-Methyl-d-Aspartate (NMDA) Antagonists for the Treatment of Depression. In: Skolnick, P. (eds) Glutamate-based Therapies for Psychiatric Disorders. Milestones in Drug Therapy. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0346-0241-9_1

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