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Ionic Glutamate Modulators in Depression (Zinc, Magnesium)

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Glutamate-based Therapies for Psychiatric Disorders

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

Abstract

Considerable evidence has accumulated over the past 10 years demonstrating an important role of zinc and magnesium, potent modulators of glutamate receptors, in depression and antidepressant treatment. Clinical reports revealed reduced serum zinc and magnesium in depression, which can be normalized by successful antidepressant treatment. A preliminary clinical study demonstrated the benefit of zinc supplementation in antidepressant therapy in both treatment nonresistant and resistant patients. The clinical efficacy of magnesium treatment was observed in major depression and depressed elderly diabetics with hypomagnesemia. Preclinical studies demonstrated antidepressant activity of zinc and magnesium in a variety of rodent tests and models of depression and suggest a causative role for zinc and magnesium deficiency in the induction of depressive-like symptoms in rodents. This chapter provides an overview of the clinical and experimental evidence that implicates zinc and magnesium in the pathophysiology and therapy of depression in the context of the glutamate hypothesis of this disease.

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References

  1. Takeda A (2000) Movement of zinc and its functional significance in the brain. Brain Res Brain Res Rev 34:137–148

    PubMed  CAS  Google Scholar 

  2. Frederickson CJ, Moncrieff DW (1994) Zinc-containing neurons. Biol Signals 3:127–139

    PubMed  CAS  Google Scholar 

  3. Frederickson CJ, Suh SW, Silva D, Frederickson CJ, Thompson RB (2000) Importance of zinc in the central nervous system: the zinc-containing neuron. J Nutr 130:1471S–1483S

    PubMed  CAS  Google Scholar 

  4. Wang Z, Li JY, Dahlstrom A, Danscher G (2001) Zinc-enriched GABAergic terminals in mouse spinal cord. Brain Res 921:165–172

    PubMed  CAS  Google Scholar 

  5. Takeda A, Tamano H (2009) Insight into zinc signaling from dietary zinc deficiency. Brain Res Rev 62:33–44

    PubMed  CAS  Google Scholar 

  6. Law W, Kelland EE, Sharp P, Toms NJ (2003) Characterisation of zinc uptake into rat cultured cerebrocortical oligodendrocyte progenitor cells. Neurosci Lett 352:113–116

    PubMed  CAS  Google Scholar 

  7. Seve M, Chimienti F, Devergnas S, Favier A (2004) In silico identification and expression of SLC30 family genes: an expressed sequence tag data mining strategy for the characterization of zinc transporters’ tissue expression. BMC Genomics 5:32

    PubMed  Google Scholar 

  8. Liuzzi JP, Cousins RJ (2004) Mammalian zinc transporters. Annu Rev Nutr 24:151–172

    PubMed  CAS  Google Scholar 

  9. Laube B (2002) Potentiation of inhibitory glycinergic neurotransmission by Zn2+: a synergistic interplay between presynaptic P2X2 and postsynaptic glycine receptors. Eur J Neurosci 16:1025–1036

    PubMed  Google Scholar 

  10. Mocchegiani E, Bertoni-Freddari C, Marcellini F, Malavolta M (2005) Brain, aging and neurodegeneration: role of zinc ion availability. Prog Neurobiol 75:367–390

    PubMed  CAS  Google Scholar 

  11. Christine CW, Choi DW (1990) Effect of zinc on NMDA receptor-mediated channel currents in cortical neurons. J Neurosci 10:108–116

    PubMed  CAS  Google Scholar 

  12. Paoletti P, Vergnano AM, Barbour B, Casado M (2009) Zinc at glutamatergic synapses. Neuroscience 158:126–136

    PubMed  CAS  Google Scholar 

  13. Chen N, Moshaver A, Raymond LA (1997) Differential sensitivity of recombinant N-methyl-d-aspartate receptor subtypes to zinc inhibition. Mol Pharmacol 51:1015–1023

    PubMed  CAS  Google Scholar 

  14. Paoletti P, Ascher P, Neyton J (1997) High-affinity zinc inhibition of NMDA NR1-NR2A receptors. J Neurosci 17:5711–5725

    PubMed  CAS  Google Scholar 

  15. Williams K (1996) Separating dual effects of zinc at recombinant N-methyl-d-aspartate receptors. Neurosci Lett 215:9–12

    PubMed  CAS  Google Scholar 

  16. Mayer ML, Vyklicky L Jr, Westbrook GL (1989) Modulation of excitatory amino acid receptors by group IIB metal cations in cultured mouse hippocampal neurones. J Physiol 415:329–350

    PubMed  CAS  Google Scholar 

  17. Rassendren FA, Lory P, Pin JP, Nargeot J (1990) Zinc has opposite effects on NMDA and non-NMDA receptors expressed in Xenopus oocytes. Neuron 4:733–740

    PubMed  CAS  Google Scholar 

  18. Dreixler JC, Leonard JP (1994) Subunit-specific enhancement of glutamate receptor response by zinc. Brain Res Mol Brain Res 22:144–150

    PubMed  CAS  Google Scholar 

  19. Hansen CR Jr, Malecha M, Mackenzie TB, Kroll J (1983) Copper and zinc deficiencies in association with depression and neurological findings. Biol Psychiatry 18:395–401

    PubMed  Google Scholar 

  20. McLoughlin IJ, Hodge JS (1990) Zinc in depressive disorder. Acta Psychiatr Scand 82:451–453

    PubMed  CAS  Google Scholar 

  21. Maes M, D’Haese PC, Scharpe S, D’Hondt P, Cosyns P, De Broe ME (1994) Hypozincemia in depression. J Affect Disord 31:135–140

    PubMed  CAS  Google Scholar 

  22. Nowak G, Zieba A, Dudek D, Krosniak M, Szymaczek M, Schlegel-Zawadzka M (1999) Serum trace elements in animal models and human depression. Part I. Zinc. Hum Psychopharmacol Clin Exp 14:83–86

    CAS  Google Scholar 

  23. Wojcik J, Dudek D, Schlegel-Zawadzka M, Grabowska M, Marcinek A, Florek E, Piekoszewski W, Nowak RJ, Opoka W, Nowak G (2006) Antepartum/postpartum depressive symptoms and serum zinc and magnesium levels. Pharmacol Rep 58:571–576

    PubMed  CAS  Google Scholar 

  24. Schlegel_Zawadzka M, Zieba A, Dudek D, Krosniak M, Szymaczek M, Nowak G (2000) Effect of depression and of antidepressant therapy on serum zinc levels – a preliminary clinical study. In: Roussel AM, Anderson RA, Favrier AE (eds) Trace elements in man and animals 10. Kluwer Academic Plenum Press, New York, pp 607–610

    Google Scholar 

  25. Anisman H, Merali Z, Poulter MO, Hayley S (2005) Cytokines as a precipitant of depressive illness: animal and human studies. Curr Pharm Des 11:963–972

    PubMed  CAS  Google Scholar 

  26. Maes M, Yirmyia R, Noraberg J, Brene S, Hibbelen J, Perini G, Kubera M, Bob P, Lerer B, Maj M (2009) The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis 24:27–53

    PubMed  CAS  Google Scholar 

  27. Srinivas U, Braconier JH, Jeppsson B, Abdulla M, Akesson B, Ockerman PA (1988) Trace element alterations in infectious diseases. Scand J Clin Lab Invest 48:495–500

    PubMed  CAS  Google Scholar 

  28. Maes M, Vandoolaeghe E, Neels H, Demedts P, Wauters A, Meltzer HY, Altamura C, Desnyder R (1997) Lower serum zinc in major depression is a sensitive marker of treatment resistance and of the immune/inflammatory response in that illness. Biol Psychiatry 42:349–358

    PubMed  CAS  Google Scholar 

  29. Nowak G, Siwek M, Dudek D, Zieba A, Pilc A (2003) Effect of zinc supplementation on antidepressant therapy in unipolar depression: a preliminary placebo-controlled study. Pol J Pharmacol 55:1143–1147

    PubMed  CAS  Google Scholar 

  30. Siwek M, Dudek D, Paul IA, Sowa-Kucma M, Zieba A, Popik P, Pilc A, Nowak G (2009) Zinc supplementation augments efficacy of imipramine in treatment resistant patients: a double blind, placebo-controlled study. J Affect Disord 118:187–195

    PubMed  CAS  Google Scholar 

  31. Nowak G, Szewczyk B, Sadlik K, Piekoszewski W, Trela F, Florek E, Pilc A (2003) Reduced potency of zinc to interact with NMDA receptors in hippocampal tissue of suicide victims. Pol J Pharmacol 55:455–459

    PubMed  CAS  Google Scholar 

  32. Kroczka B, Branski P, Palucha A, Pilc A, Nowak G (2001) Antidepressant-like properties of zinc in rodent forced swim test. Brain Res Bull 55:297–300

    PubMed  CAS  Google Scholar 

  33. Kroczka B, Zieba A, Dudek D, Pilc A, Nowak G (2000) Zinc exhibits an antidepressant-like effect in the forced swimming test in mice. Pol J Pharmacol 52:403–406

    PubMed  CAS  Google Scholar 

  34. Nowak G, Szewczyk B, Wieronska JM, Branski P, Palucha A, Pilc A, Sadlik K, Piekoszewski W (2003) Antidepressant-like effects of acute and chronic treatment with zinc in forced swim test and olfactory bulbectomy model in rats. Brain Res Bull 61:159–164

    PubMed  CAS  Google Scholar 

  35. Rosa AO, Lin J, Calixto JB, Santos AR, Rodrigues AL (2003) Involvement of NMDA receptors and L-arginine-nitric oxide pathway in the antidepressant-like effects of zinc in mice. Behav Brain Res 144:87–93

    PubMed  CAS  Google Scholar 

  36. Franco JL, Posser T, Brocardo PS, Trevisan R, Uliano-Silva M, Gabilan NH, Santos AR, Leal RB, Rodrigues AL, Farina M, Dafre AL (2008) Involvement of glutathione ERK1/2 phosphorylation and BDNF expression in the antidepressant-like effect of zinc in rats. Behav Brain Res 188:316–323

    PubMed  CAS  Google Scholar 

  37. Cunha MP, Machado DG, Bettio LE, Capra JC, Rodrigues AL (2008) Interaction of zinc with antidepressants in the tail suspension test. Prog Neuropsychopharmacol Biol Psychiatry 32:1913–1920

    PubMed  CAS  Google Scholar 

  38. Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM (2002) Neurobiology of depression. Neuron 34:13–25

    PubMed  CAS  Google Scholar 

  39. 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 

  40. Song C, Leonard BE (2005) The olfactory bulbectomised rat as a model of depression. Neurosci Biobehav Rev 29:627–647

    PubMed  Google Scholar 

  41. van Riezen H, Leonard BE (1990) Effects of psychotropic drugs on the behavior and neurochemistry of olfactory bulbectomized rats. Pharmacol Ther 47:21–34

    PubMed  Google Scholar 

  42. Papp M, Moryl E, Willner P (1996) Pharmacological validation of the chronic mild stress model of depression. Eur J Pharmacol 296:129–136

    PubMed  CAS  Google Scholar 

  43. Sowa-Kucma M, Legutko B, Szewczyk B, Novak K, Znojek P, Poleszak E, Papp M, Pilc A, Nowak G (2008) Antidepressant-like activity of zinc: further behavioral and molecular evidence. J Neural Transm 115:1621–1628

    PubMed  CAS  Google Scholar 

  44. Sanchez C, Gruca P, Papp M (2003) R-citalopram counteracts the antidepressant-like effect of escitalopram in a rat chronic mild stress model. Behav Pharmacol 14:465–470

    PubMed  CAS  Google Scholar 

  45. Cieslik K, Klenk-Majewska B, Danilczuk Z, Wrobel A, Lupina T, Ossowska G (2007) Influence of zinc supplementation on imipramine effect in a chronic unpredictable stress (CUS) model in rats. Pharmacol Rep 59:46–52

    PubMed  CAS  Google Scholar 

  46. Ossowska G, Zebrowska-Lupina I, Danilczuk Z, Klenk-Majewska B (2002) Repeated treatment with selective serotonin reuptake inhibitors but not anxiolytics prevents the stress-induced deficit of fighting behavior. Pol J Pharmacol 54:373–380

    PubMed  CAS  Google Scholar 

  47. Szewczyk B, Branski P, Wieronska JM, Palucha A, Pilc A, Nowak G (2002) Interaction of zinc with antidepressants in the forced swimming test in mice. Pol J Pharmacol 54:681–685

    PubMed  CAS  Google Scholar 

  48. Szewczyk B, Poleszak E, Wlaz P, Wrobel A, Blicharska E, Cichy A, Dybala M, Siwek A, Pomierny-Chamiolo L, Piotrowska A, Branski P, Pilc A, Nowak G (2009) The involvement of serotonergic system in the antidepressant effect of zinc in the forced swim test. Prog Neuropsychopharmacol Biol Psychiatry 33:323–329

    PubMed  CAS  Google Scholar 

  49. Tassabehji NM, Corniola RS, Alshingiti A, Levenson CW (2008) Zinc deficiency induces depression-like symptoms in adult rats. Physiol Behav 95:365–369

    PubMed  CAS  Google Scholar 

  50. Whittle N, Lubec G, Singewald N (2009) Zinc deficiency induces enhanced depression-like behaviour and altered limbic activation reversed by antidepressant treatment in mice. Amino Acids 36:147–158

    PubMed  CAS  Google Scholar 

  51. Tamano H, Kan F, Kawamura M, Oku N, Takeda A (2009) Behavior in the forced swim test and neurochemical changes in the hippocampus in young rats after 2-week zinc deprivation. Neurochem Int 55:536–541

    PubMed  CAS  Google Scholar 

  52. Watanabe M, Tamano H, Kikuchi T, Takeda A (2009) Susceptibility to stress in young rats after 2-week zinc deprivation. Neurochem Int. doi:10.1016/j.neuint.2009.11.014

    Google Scholar 

  53. Takeda A, Tamano H, Kan F, Itoh H, Oku N (2007) Anxiety-like behavior of young rats after 2-week zinc deprivation. Behav Brain Res 177:1–6

    PubMed  CAS  Google Scholar 

  54. Gombos Z, Spiller A, Cottrell GA, Racine RJ, McIntyre BW (1999) Mossy fiber sprouting induced by repeated electroconvulsive shock seizures. Brain Res 844:28–33

    PubMed  CAS  Google Scholar 

  55. Vaidya VA, Siuciak JA, Du F, Duman RS (1999) Hippocampal mossy fiber sprouting induced by chronic electroconvulsive seizures. Neuroscience 89:157–166

    PubMed  CAS  Google Scholar 

  56. Lamont SR, Paulls A, Stewart CA (2001) Repeated electroconvulsive stimulation, but not antidepressant drugs, induces mossy fibre sprouting in the rat hippocampus. Brain Res 893:53–58

    PubMed  CAS  Google Scholar 

  57. Szewczyk B, Sowa M, Czupryn A, Wieronska JM, Branski P, Sadlik K, Opoka W, Piekoszewski W, Smialowska M, Skangiel-Kramska J, Pilc A, Nowak G (2006) Increase in synaptic hippocampal zinc concentration following chronic but not acute zinc treatment in rats. Brain Res 1090:69–75

    PubMed  CAS  Google Scholar 

  58. Opoka W, Sowa-Kucma M, Kowalska M, Bas B, Golembiowska K, Nowak G (2008) Intraperitoneal zinc administration increases extracellular zinc in the rat prefrontal cortex. J Physiol Pharmacol 59:477–487

    PubMed  CAS  Google Scholar 

  59. Nowak G, Schlegel-Zawadzka M (1999) Alterations in serum and brain trace element levels after antidepressant treatment. Part I. Zinc. Biol Trace Elem Res 67:85–92

    PubMed  CAS  Google Scholar 

  60. Bresink I, Danysz W, Parsons CG, Mutschler E (1995) Different binding affinities of NMDA receptor channel blockers in various brain regions-indication of NMDA receptor heterogeneity. Neuropharmacology 34:533–540

    PubMed  CAS  Google Scholar 

  61. Szewczyk B, Kata R, Nowak G (2001) Rise in zinc affinity for the NMDA receptor evoked by chronic imipramine is species-specific. Pol J Pharmacol 53:641–645

    PubMed  CAS  Google Scholar 

  62. Szewczyk B, Poleszak E, Sowa-Kucma M, Wrobel A, Slotwinski S, Listos J, Wlaz P, Cichy A, Siwek M, Dybala M, Golembiowska K, Pilc A, Nowak G (2010) The involvement of NMDA and AMPA receptors in the mechanism of antidepressant-like action of zinc in forced swim test. Amino Acids 39:205–217

    PubMed  Google Scholar 

  63. Poleszak E, Szewczyk B, Wlaz A, Fidecka S, Wlaz P, Pilc A, Nowak G (2008) d-serine, a selective glycine/N-methyl-d-aspartate receptor agonist, antagonizes the antidepressant-like effects of magnesium and zinc in mice. Pharmacol Rep 60:996–1000

    PubMed  CAS  Google Scholar 

  64. 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 

  65. Cichy A, Sowa-Kucma M, Legutko B, Pomierny-Chamiolo L, Siwek A, Piotrowska A, Szewczyk B, Poleszak E, Pilc A, Nowak G (2009) Zinc-induced adaptive changes in NMDA/glutamatergic and serotonergic receptors. Pharmacol Rep 61:1184–1191

    PubMed  CAS  Google Scholar 

  66. Mittal CK, Harrell WB, Mehta CS (1995) Interaction of heavy metal toxicants with brain constitutive nitric oxide synthase. Mol Cell Biochem 149–150:263–265

    PubMed  Google Scholar 

  67. Duman RS (2004) Role of neurothropic factors in the etiology and treatment of mood disorders. Neuromolecular Med 5:11–25

    PubMed  CAS  Google Scholar 

  68. Schmidt HD, Duman RS (2007) The role of neurotrophic factors in adult hippocampal neurogenesis, antidepressant treatments and animal models of depressive-like behavior. Behav Pharmacol 18:391–418

    PubMed  CAS  Google Scholar 

  69. Nowak G, Legutko B, Szewczyk B, Papp M, Sanak M, Pilc A (2004) Zinc treatment induces cortical brain-derived neurotrophic factor gene expression. Eur J Pharmacol 492:57–59

    PubMed  CAS  Google Scholar 

  70. Embi N, Rylatt DB, Cohen P (1980) Glycogen synthase kinase-3 from rabbit skeletal muscle. Separation from cyclic-AMP-dependent protein kinase and phosphorylase kinase. Eur J Biochem 107:519–527

    PubMed  CAS  Google Scholar 

  71. Kaidanovich-Beilin O, Milman A, Weizman A, Pick CG, Eldar-Finkelman H (2004) Rapid antidepressive-like activity of specific glycogen synthase kinase-3 inhibitor and its effect on beta-catenin in mouse hippocampus. Biol Psychiatry 55:781–784

    PubMed  CAS  Google Scholar 

  72. Gould TD, Manji HK (2005) Glycogen synthase kinase-3: a putative molecular target for lithium mimetic drugs. Neuropsychopharmacology 30:1223–1237

    PubMed  CAS  Google Scholar 

  73. Ilouz R, Kaidanovich O, Gurwitz D, Eldar-Finkelman H (2002) Inhibition of glycogen synthase kinase-3beta by bivalent zinc ions: insight into the insulin-mimetic action of zinc. Biochem Biophys Res Commun 295:102–106

    PubMed  CAS  Google Scholar 

  74. Szewczyk B, Poleszak E, Sowa-Kucma M, Siwek M, Dudek D, Ryszewska-Pokrasniewicz B, Radziwon-Zaleska M, Opoka W, Czekaj J, Pilc A, Nowak G (2008) Antidepressant activity of zinc and magnesium in view of the current hypothesis of antidepressant action. Pharmacol Rep 60:588–589

    PubMed  CAS  Google Scholar 

  75. Murphy E (2000) Mysteries of magnesium homeostasis. Circ Res 86:245–248

    PubMed  CAS  Google Scholar 

  76. Touyz RM (2004) Magnesium in clinical medicine. Front Biosci 9:1278–1293

    PubMed  CAS  Google Scholar 

  77. Romani AM, Scarpa A (2000) Regulation of cellular magnesium. Front Biosci 5:D720–D734

    PubMed  CAS  Google Scholar 

  78. Altura BM (1994) Introduction: importance of Mg in physiology and medicine and the need for ion selective electrodes. Scand J Clin Lab Invest Suppl 217:5–9

    PubMed  CAS  Google Scholar 

  79. Morris ME (1992) Brain and CSF magnesium concentrations during magnesium deficit in animals and humans: neurological symptoms. Magnes Res 5:303–313

    PubMed  CAS  Google Scholar 

  80. Murck H (2002) Magnesium and affective disorders. Nutr Neurosci 5:375–389

    PubMed  CAS  Google Scholar 

  81. Ryan MF (1991) The role of magnesium in clinical biochemistry: an overview. Ann Clin Biochem 28(Pt 1):19–26

    PubMed  Google Scholar 

  82. Wolf FI, Trapani V, Cittadini A (2008) Magnesium and the control of cell proliferation: looking for a needle in a haystack. Magnes Res 21:83–91

    PubMed  CAS  Google Scholar 

  83. Yang ZW, Wang J, Zheng T, Altura BT, Altura BM (2000) Low [Mg(2+)](o) induces contraction and [Ca(2+)](i) rises in cerebral arteries: roles of ca(2+), PKC, and PI3. Am J Physiol Heart Circ Physiol 279:H2898–H2907

    PubMed  CAS  Google Scholar 

  84. Mayer ML, Westbrook GL, Guthrie PB (1984) Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones. Nature 309:261–263

    PubMed  CAS  Google Scholar 

  85. Weston PG (1921) Magnesium as a sedative. Am J Psychiatry 278:637–638

    Google Scholar 

  86. Frizel D, Coppen A, Marks V (1969) Plasma magnesium and calcium in depression. Br J Psychiatry 115:1375–1377

    PubMed  CAS  Google Scholar 

  87. Linder J, Brismar K, Beck-Friis J, Saaf J, Wetterberg L (1989) Calcium and magnesium concentrations in affective disorder: difference between plasma and serum in relation to symptoms. Acta Psychiatr Scand 80:527–537

    PubMed  CAS  Google Scholar 

  88. Hashizume N, Mori M (1990) An analysis of hypermagnesemia. Jpn J Med 29:368–372

    PubMed  CAS  Google Scholar 

  89. Zieba A, Kata R, Dudek D, Schlegel-Zawadzka M, Nowak G (2000) Serum trace elements in animal models and human depression: Part III. Magnesium. Relationship with copper. Hum Psychopharmacol 15:631–635

    PubMed  CAS  Google Scholar 

  90. Nechifor M (2008) Interactions between magnesium and psychotropic drugs. Magnes Res 21:97–100

    PubMed  CAS  Google Scholar 

  91. Barragan-Rodriguez L, Rodriguez-Moran M, Guerrero-Romero F (2007) Depressive symptoms and hypomagnesemia in older diabetic subjects. Arch Med Res 38:752–756

    PubMed  CAS  Google Scholar 

  92. Banki CM, Vojnik M, Papp Z, Balla KZ, Arato M (1985) Cerebrospinal fluid magnesium and calcium related to amine metabolites, diagnosis, and suicide attempts. Biol Psychiatry 20:163–171

    PubMed  CAS  Google Scholar 

  93. Kirov GK, Birch NJ, Steadman P, Ramsey RG (1994) Plasma magnesium levels in a population of psychiatric patients: correlations with symptoms. Neuropsychobiology 30:73–78

    PubMed  CAS  Google Scholar 

  94. Young LT, Robb JC, Levitt AJ, Cooke RG, Joffe RT (1996) Serum Mg2+ and Ca2+/Mg2+ ratio in major depressive disorder. Neuropsychobiology 34:26–28

    PubMed  CAS  Google Scholar 

  95. Frazer A, Ramsey TA, Swann A, Bowden C, Brunswick D, Garver D, Secunda S (1983) Plasma and erythrocyte electrolytes in affective disorders. J Affect Disord 5:103–113

    PubMed  CAS  Google Scholar 

  96. Widmer J, Bovier P, Karege F, Raffin Y, Hilleret H, Gaillard JM, Tissot R (1992) Evolution of blood magnesium, sodium and potassium in depressed patients followed for three months. Neuropsychobiology 26:173–179

    PubMed  CAS  Google Scholar 

  97. Widmer J, Henrotte JG, Raffin Y, Bovier P, Hilleret H, Gaillard JM (1995) Relationship between erythrocyte magnesium, plasma electrolytes and cortisol and intensity of symptoms in major depressed patients. J Affect Disord 34:201–209

    PubMed  CAS  Google Scholar 

  98. Linder J, Fyro B, Pettersson U, Werner S (1989) Acute antidepressant effect of lithium is associated with fluctuation of calcium and magnesium in plasma. A double-blind study on the antidepressant effect of lithium and clomipramine. Acta Psychiatr Scand 80:27–36

    PubMed  CAS  Google Scholar 

  99. Eby GA, Eby KL (2006) Rapid recovery from major depression using magnesium treatment. Med Hypotheses 67:362–370

    PubMed  CAS  Google Scholar 

  100. Barragan-Rodriguez L, Rodriguez-Moran M, Guerrero-Romero F (2008) Efficacy and safety of oral magnesium supplementation in the treatment of depression in the elderly with type 2 diabetes: a randomized, equivalent trial. Magnes Res 21:218–223

    PubMed  CAS  Google Scholar 

  101. Pavlinac D, Langer R, Lenhard L, Deftos L (1979) Magnesium in affective disorders. Biol Psychiatry 14:657–661

    PubMed  CAS  Google Scholar 

  102. Chouinard G, Beauclair L, Geiser R, Etienne P (1990) A pilot study of magnesium aspartate hydrochloride (Magnesiocard) as a mood stabilizer for rapid cycling bipolar affective disorder patients. Prog Neuropsychopharmacol Biol Psychiatry 14:171–180

    PubMed  CAS  Google Scholar 

  103. Cox IM, Campbell MJ, Dowson D (1991) Red blood cell magnesium and chronic fatigue syndrome. Lancet 337:757–760

    PubMed  CAS  Google Scholar 

  104. Heiden A, Frey R, Presslich O, Blasbichler T, Smetana R, Kasper S (1999) Treatment of severe mania with intravenous magnesium sulphate as a suppplementary therapy. Psychiatry Res 89:239–246

    PubMed  CAS  Google Scholar 

  105. Singewald N, Sinner C, Hetzenauer A, Sartori SB, Murck H (2004) Magnesium-deficient diet alters depression- and anxiety-related behavior in mice – influence of desipramine and Hypericum perforatum extract. Neuropharmacology 47:1189–1197

    PubMed  CAS  Google Scholar 

  106. Kantak KM (1988) Magnesium deficiency alters aggressive behavior and catecholamine function. Behav Neurosci 102:304–311

    PubMed  CAS  Google Scholar 

  107. Henrotte JG, Franck G, Santarromana M, Frances H, Mouton D, Motta R (1997) Mice selected for low and high blood magnesium levels: a new model for stress studies. Physiol Behav 61:653–658

    PubMed  CAS  Google Scholar 

  108. Decollogne S, Tomas A, Lecerf C, Adamowicz E, Seman M (1997) NMDA receptor complex blockade by oral administration of magnesium: comparison with MK-801. Pharmacol Biochem Behav 58:261–268

    PubMed  CAS  Google Scholar 

  109. Poleszak E, Szewczyk B, Kedzierska E, Wlaz P, Pilc A, Nowak G (2004) Antidepressant- and anxiolytic-like activity of magnesium in mice. Pharmacol Biochem Behav 78:7–12

    PubMed  CAS  Google Scholar 

  110. Poleszak E, Wlaz P, Kedzierska E, Radziwon-Zaleska M, Pilc A, Fidecka S, Nowak G (2005) Effects of acute and chronic treatment with magnesium in the forced swim test in rats. Pharmacol Rep 57:654–658

    PubMed  CAS  Google Scholar 

  111. Poleszak E, Wlaz P, Kedzierska E, Nieoczym D, Wrobel A, Fidecka S, Pilc A, Nowak G (2007) NMDA/glutamate mechanism of antidepressant-like action of magnesium in forced swim test in mice. Pharmacol Biochem Behav 88:158–164

    PubMed  CAS  Google Scholar 

  112. Cardoso CC, Lobato KR, Binfare RW, Ferreira PK, Rosa AO, Santos AR, Rodrigues AL (2009) Evidence for the involvement of the monoaminergic system in the antidepressant-like effect of magnesium. Prog Neuropsychopharmacol Biol Psychiatry 33:235–242

    PubMed  CAS  Google Scholar 

  113. Poleszak E, Wlaz P, Szewczyk B, Kedzierska E, Wyska E, Librowski T, Szymura-Oleksiak J, Fidecka S, Pilc A, Nowak G (2005) Enhancement of antidepressant-like activity by joint administration of imipramine and magnesium in the forced swim test: behavioral and pharmacokinetic studies in mice. Pharmacol Biochem Behav 81:524–529

    PubMed  CAS  Google Scholar 

  114. Poleszak E (2008) Benzodiazepine/GABA(A) receptors are involved in magnesium-induced anxiolytic-like behavior in mice. Pharmacol Rep 60:483–489

    PubMed  CAS  Google Scholar 

  115. Nowak L, Bregestovski P, Ascher P, Herbet A, Prochiantz A (1984) Magnesium gates glutamate-activated channels in mouse central neurones. Nature 307:462–465

    PubMed  CAS  Google Scholar 

  116. Poleszak E (2007) Modulation of antidepressant-like activity of magnesium by serotonergic system. J Neural Transm 114:1129–1134

    PubMed  CAS  Google Scholar 

  117. DeVinney R, Wang HH (1995) Mg 2+ enhances high affinity [3H]8-hydroxy-2-(di-n-propylamino) tetralin binding and guanine nucleotide modulation of serotonin -1a receptors. J Recept Signal Transduct Res 15:757–771

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343, Kraków, Poland

    Gabriel Nowak

  2. Department of Cytobiology, Collegium Medicum, Jagiellonian University, Medyczna 9, PL 30-688, Kraków, Poland

    Gabriel Nowak

Authors
  1. Bernadeta Szewczyk
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  2. Ewa Poleszak
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  3. Andrzej Pilc
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  4. Gabriel Nowak
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Corresponding author

Correspondence to Gabriel Nowak .

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Editors and Affiliations

  1. Div Pharmacotherapies & Medical Conseque, National Institute on Drug Abuse, Executive Boulevard 6001, Rockville, 20852, Maryland, USA

    Phil Skolnick

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© 2010 Birkhäuser Basel

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Szewczyk, B., Poleszak, E., Pilc, A., Nowak, G. (2010). Ionic Glutamate Modulators in Depression (Zinc, Magnesium). 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_2

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