Nitric Oxide Signaling in Depression and Antidepressant Action



The pathogenesis of mood disorders remains elusive, but it is evident that multiple factors, genetic and environmental, play a crucial role for adult psychopathology and neurobiology. With regard to therapy, a significant proportion of affective disorder patients are partial or nonresponders, and there has been no major breakthrough in finding novel effective drug targets since the introduction of the current marketed antidepressant drugs in the 1950s to the 1980s, which all are based on monoaminergic pharmacological effects. Consequently, there exists a pressing need to develop novel treatment strategies – and ultimately understand the etiology and pathophysiology of affective disorders.

Nitric oxide serves an important role in the nervous system, where it acts as a messenger molecule in a number of physiological processes, including processes being linked to the major psychiatric diseases. This chapter will review general aspects of the NO system in major depressive disorder (MDD), as well as focus on the inhibition of NO production as putative therapeutic agents toward depression.


Methylene Blue NMDA Receptor Major Depressive Disorder Force Swim Test Taste Aversion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



GW was supported by the Danish Medical Research Council (Grant 11-107897) and the AU-IDEAS Initiative (eMOOD). SJ was supported by CNPq and FAPESP.

Conflicts of Interest

SJ declare no conflicts of interest. GW has received honorarium from H. Lundbeck A/S, AstraZeneca AB, Servier A/S, and Eli Lilly A/S.


  1. 1.
    Abu-Ghanem Y, Cohen H, Buskila Y, Grauer E, Amitai Y. Enhanced stress reactivity in nitric oxide synthase type 2 mutant mice: findings in support of astrocytic nitrosative modulation of behavior. Neuroscience. 2008;156:257–65.CrossRefPubMedGoogle Scholar
  2. 2.
    Adachi M, Barrot M, Autry AE, Theobald D, Monteggia LM. Selective loss of brain-derived neurotrophic factor in the dentate gyrus attenuates antidepressant efficacy. Biol Psychiatry. 2008;63:642–9.CrossRefPubMedGoogle Scholar
  3. 3.
    Aktan F. iNOS-mediated nitric oxide production and its regulation. Life Sci. 2004;75:639–53.CrossRefPubMedGoogle Scholar
  4. 4.
    Akyol O, Zoroglu SS, Armutcu F, Sahin S, Gurel A. Nitric oxide as a physiopathological factor in neuropsychiatric disorders. In Vivo. 2004;18:377–90.PubMedGoogle Scholar
  5. 5.
    Alda M (2008) NCT00214877: methylene blue for cognitive dysfunction in bipolar disorder. vol. 2010: Scholar
  6. 6.
    Amitai Y. Physiologic role for “inducible” nitric oxide synthase: a new form of astrocytic-neuronal interface. Glia. 2010;58:1775–81.CrossRefPubMedGoogle Scholar
  7. 7.
    Arancio O, Lev-Ram V, Tsien RY, Kandel ER, Hawkins RD. Nitric oxide acts as a retrograde messenger during long-term potentiation in cultured hippocampal neurons. J Physiol Paris. 1996;90:321–2.CrossRefPubMedGoogle Scholar
  8. 8.
    Arevalo R, Sanchez F, Alonso JR, Carretero J, Vazquez R, Aijon J. NADPH-diaphorase activity in the hypothalamic magnocellular neurosecretory nuclei of the rat. Brain Res Bull. 1992;28:599–603.CrossRefPubMedGoogle Scholar
  9. 9.
    Aricioglu F, Altunbas H. Is agmatine an endogenous anxiolytic/antidepressant agent? Ann N Y Acad Sci. 2003;1009:136–40.CrossRefPubMedGoogle Scholar
  10. 10.
    Arlt S, Schulze F, Eichenlaub M, Maas R, Lehmbeck JT, Schwedhelm E, Jahn H, Boger RH. Asymmetrical dimethylarginine is increased in plasma and decreased in cerebrospinal fluid of patients with Alzheimer’s disease. Dement Geriatr Cogn Disord. 2008;26:58–64.CrossRefPubMedGoogle Scholar
  11. 11.
    Assreuy J, Cunha FQ, Liew FY, Moncada S. Feedback inhibition of nitric oxide synthase activity by nitric oxide. Br J Pharmacol. 1993;108:833–7.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Autry AE, Monteggia LM. Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacol Rev. 2012;64:238–58.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Babbedge RC, Bland-Ward PA, Hart SL, Moore PK. Inhibition of rat cerebellar nitric oxide synthase by 7-nitro indazole and related substituted indazoles. Br J Pharmacol. 1993;110:225–8.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Bagley J, Moghaddam B. Temporal dynamics of glutamate efflux in the prefrontal cortex and in the hippocampus following repeated stress: effects of pretreatment with saline or diazepam. Neuroscience. 1997;77:65–73.CrossRefPubMedGoogle Scholar
  15. 15.
    Bannerman DM, Chapman PF, Kelly PA, Butcher SP, Morris RG. Inhibition of nitric oxide synthase does not impair spatial learning. J Neurosci. 1994;14:7404–14.PubMedGoogle Scholar
  16. 16.
    Bannerman DM, Chapman PF, Kelly PA, Butcher SP, Morris RG. Inhibition of nitric oxide synthase does not prevent the induction of long-term potentiation in vivo. J Neurosci. 1994;14:7415–25.PubMedGoogle Scholar
  17. 17.
    Barjavel MJ, Bhargava HN. Nitric oxide synthase activity in brain regions and spinal cord of mice and rats: kinetic analysis. Pharmacology. 1995;50:168–74.CrossRefPubMedGoogle Scholar
  18. 18.
    Barragán-Rodríguez L, Rodríguez-Morán M, Guerrero-Romero F. 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. 2008;21:218–23.PubMedGoogle Scholar
  19. 19.
    Beckman JS. The physiological and pathological chemistry of nitric oxide. In: Lancaster J, editor. Nitric oxide: principles and actions. San Diego: Academic; 1996. p. 1–82.CrossRefGoogle Scholar
  20. 20.
    Beneyto M, Kristiansen LV, Oni-Orisan A, McCullumsmith RE, Meador-Woodruff JH. Abnormal glutamate receptor expression in the medial temporal lobe in schizophrenia and mood disorders. Neuropsychopharmacology. 2007;32:1888–902.CrossRefPubMedGoogle Scholar
  21. 21.
    Bernstein HG, Heinemann A, Krell D, Mawrin C, Bielau H, Danos P, Diekmann S, Keilhoff G, Bogerts B, Baumann B. Further immunohistochemical evidence for impaired NO signaling in the hypothalamus of depressed patients. Ann N Y Acad Sci. 2002;973:91–3.CrossRefPubMedGoogle Scholar
  22. 22.
    Bernstein HG, Stanarius A, Baumann B, Henning H, Krell D, Danos P, Falkai P, Bogerts B. Nitric oxide synthase-containing neurons in the human hypothalamus: reduced number of immunoreactive cells in the paraventricular nucleus of depressive patients and schizophrenics. Neuroscience. 1998;83:867–75.CrossRefPubMedGoogle Scholar
  23. 23.
    Bhat G, Mahesh VB, Aguan K, Brann DW. Evidence that brain nitric oxide synthase is the major nitric oxide synthase isoform in the hypothalamus of the adult female rat and that nitric oxide potently regulates hypothalamic cGMP levels. Neuroendocrinology. 1996;64:93–102.CrossRefPubMedGoogle Scholar
  24. 24.
    Bilbo SD, Hotchkiss AK, Chiavegatto S, Nelson RJ. Blunted stress responses in delayed type hypersensitivity in mice lacking the neuronal isoform of nitric oxide synthase. J Neuroimmunol. 2003;140:41–8.CrossRefPubMedGoogle Scholar
  25. 25.
    Bliss TVP, Collingridge GL. A synaptic model of memory: long-term potentiation in the hippocampus. Nature. 1993;361:31–9.CrossRefPubMedGoogle Scholar
  26. 26.
    Blottner D, Grozdanovic Z, Gossrau R. Histochemistry of nitric oxide synthase in the nervous system. Histochem J. 1995;27:785–811.CrossRefPubMedGoogle Scholar
  27. 27.
    Bodoni P. Le bleu de méthylène comme calmant chez le aliénés. Sem Méd. 1899;7:56.Google Scholar
  28. 28.
    Boger RH, Diemert A, Schwedhelm E, Luneburg N, Maas R, Hecher K. The role of nitric oxide synthase inhibition by asymmetric dimethylarginine in the pathophysiology of preeclampsia. Gynecol Obstet Invest. 2009;69:1–13.PubMedGoogle Scholar
  29. 29.
    Boger RH, Maas R, Schulze F, Schwedhelm E. Asymmetric dimethylarginine (ADMA) as a prospective marker of cardiovascular disease and mortality-an update on patient populations with a wide range of cardiovascular risk. Pharmacol Res. 2009;60:7.Google Scholar
  30. 30.
    Boger RH, Sullivan LM, Schwedhelm E, Wang TJ, Maas R, Benjamin EJ, Schulze F, Xanthakis V, Benndorf RA, Vasan RS. Plasma asymmetric dimethylarginine and incidence of cardiovascular disease and death in the community. Circulation. 2009;119:1592–600.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Bohme GA, Bon C, Lemaire M, Reibaud M, Piot O, Stutzmann JM, Doble A, Blanchard JC. Altered synaptic plasticity and memory formation in nitric oxide synthase inhibitor-treated rats. Proc Natl Acad Sci U S A. 1993;90:9191–4.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Bonanno G, Giambelli R, Raiteri L, Tiraboschi E, Zappettini S, Musazzi L, Raiteri M, Racagni G, Popoli M. Chronic antidepressants reduce depolarization-evoked glutamate release and protein interactions favoring formation of SNARE complex in hippocampus. J Neurosci. 2005;25:3270–9.CrossRefPubMedGoogle Scholar
  33. 33.
    Borda T, Genaro A, Sterin-Borda L, Cremaschi G. Involvement of endogenous nitric oxide signalling system in brain muscarinic acetylcholine receptor activation. J Neural Transm. 1998;105:193–204.CrossRefPubMedGoogle Scholar
  34. 34.
    Bredt DS, Snyder SH. Nitric oxide mediates glutamate-linked enhancement of cGMP levels in the cerebellum. Proc Natl Acad Sci U S A. 1989;86:9030–3.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Bredt DS, Snyder SH. Nitric oxide: a physiologic messenger molecule. Annu Rev Biochem. 1994;63:175–95.CrossRefPubMedGoogle Scholar
  36. 36.
    Brenman JE, Bredt DS. Synaptic signaling by nitric oxide. Curr Opin Neurobiol. 1997;7:374–8.CrossRefPubMedGoogle Scholar
  37. 37.
    Brink CB, Clapton JD, Eagar BE, Harvey BH. Appearance of antidepressant-like effect by sildenafil in rats after central muscarinic receptor blockade: evidence from behavioural and neuro-receptor studies. J Neural Transm. 2008;115:117–25.CrossRefPubMedGoogle Scholar
  38. 38.
    Buga GM, Griscavage JM, Rogers NE, Ignarro LJ. Negative feedback regulation of endothelial cell function by nitric oxide. Circ Res. 1993;73:808–12.CrossRefPubMedGoogle Scholar
  39. 39.
    Buskila Y, Abu-Ghanem Y, Levi Y, Moran A, Grauer E, Amitai Y. Enhanced astrocytic nitric oxide production and neuronal modifications in the neocortex of a NOS2 mutant mouse. PLoS One. 2007;2:e843.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Buskila Y, Amitai Y. Astrocytic iNOS-dependent enhancement of synaptic release in mouse neocortex. J Neurophysiol. 2010;103:1322–8.CrossRefPubMedGoogle Scholar
  41. 41.
    Buttenschon HN, Mors O, Ewald H, McQuillin A, Kalsi G, Lawrence J, Gurling H, Kruse TA. No association between a neuronal nitric oxide synthase (NOS1) gene polymorphism on chromosome 12q24 and bipolar disorder. Am J Med Genet B Neuropsychiatr Genet. 2004;124:73–5.CrossRefGoogle Scholar
  42. 42.
    Canossa M, Giordano E, Cappello S, Guarnieri C, Ferri S. Nitric oxide down-regulates brain-derived neurotrophic factor secretion in cultured hippocampal neurons. Proc Natl Acad Sci U S A. 2002;99:3282–7.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science. 2003;301:386–9.CrossRefPubMedGoogle Scholar
  44. 44.
    Ceccatelli S, Grandison L, Scott REM, Pfaff DW, Kow LM. Estradiol regulation of nitric oxide synthase mRNAs in rat hypothalamus. Neuroendocrinology. 1996;64:357–63.CrossRefPubMedGoogle Scholar
  45. 45.
    Chanrion B, Mannoury La Cour C, Bertaso F, Lerner-Natoli M, Freissmuth M, Millan MJ, Bockaert J, Marin P. Physical interaction between the serotonin transporter and neuronal nitric oxide synthase underlies reciprocal modulation of their activity. Proc Natl Acad Sci U S A. 2007;104:8119–24.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Chapman PF, Atkins CM, Allen MT, Haley JE, Steinmetz JE. Inhibition of nitric oxide synthesis impairs two different forms of learning. Neuroreport. 1992;3:567–70.CrossRefPubMedGoogle Scholar
  47. 47.
    Chen M, Cheng C, Yan M, Niu S, Gao S, Shi S, Liu H, Qin Y, Shen A. Involvement of CAPON and nitric oxide synthases in rat muscle regeneration after peripheral nerve injury. J Mol Neurosci. 2008;34:89–100.CrossRefPubMedGoogle Scholar
  48. 48.
    Chiavegatto S, Dawson VL, Mamounas LA, Koliatsos VE, Dawson TM, Nelson RJ. Brain serotonin dysfunction accounts for aggression in male mice lacking neuronal nitric oxide synthase. Proc Natl Acad Sci U S A. 2001;98:1277–81.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Chrapko W, Jurasz P, Radomski MW, Archer SL, Newman SC, Baker G, Lara N, Le Melledo JM. Alteration of decreased plasma NO metabolites and platelet NO synthase activity by paroxetine in depressed patients. Neuropsychopharmacology. 2006;31:1286–93.PubMedGoogle Scholar
  50. 50.
    Chrapko WE, Jurasz P, Radomski MW, Lara N, Archer SL, Le Melledo JM. Decreased platelet nitric oxide synthase activity and plasma nitric oxide metabolites in major depressive disorder. Biol Psychiatry. 2004;56:129–34.CrossRefPubMedGoogle Scholar
  51. 51.
    Christopherson KS, Hillier BJ, Lim WA, Bredt DS. PSD-95 assembles a ternary complex with the N-methyl-D-aspartic acid receptor and a bivalent neuronal NO synthase PDZ domain. J Biol Chem. 1999;274:27467–73.CrossRefPubMedGoogle Scholar
  52. 52.
    Cobb BL, Ryan KL, Frei MR, Guel-Gomez V, Mickley GA. Chronic administration of L-NAME in drinking water alters working memory in rats. Brain Res Bull. 1995;38:203–7.CrossRefPubMedGoogle Scholar
  53. 53.
    Contestabile A. Roles of NMDA receptor activity and nitric oxide production in brain development. Brain Res Rev. 2000;32:476–509.CrossRefPubMedGoogle Scholar
  54. 54.
    Corbett JA, McDaniel ML. The use of aminoguanidine, a selective iNOS inhibitor, to evaluate the role of nitric oxide in the development of autoimmune diabetes. Methods. 1996;10:21–30.CrossRefPubMedGoogle Scholar
  55. 55.
    Costa A, Trainer P, Besser M, Grossman A. Nitric oxide modulates the release of corticotropin-releasing hormone from the rat hypothalamus in vitro. Brain Res. 1993;605:187–92.CrossRefPubMedGoogle Scholar
  56. 56.
    Cui H, Hayashi A, Sun HS, Belmares MP, Cobey C, Phan T, Schweizer J, Salter MW, Yu TW, Tasker RA, Garman D, Rabinowitz J, Lu PS, Tymianski M. PDZ protein interactions underlying NMDA receptor-mediated excitotoxicity and neuroprotection by PSD-95 inhibitors. J Neurosci. 2007;27:9901–15.CrossRefPubMedGoogle Scholar
  57. 57.
    da Silva GD, Matteussi AS, dos Santos AR, Calixto JB, Rodrigues AL. Evidence for dual effects of nitric oxide in the forced swimming test and in the tail suspension test in mice. Neuroreport. 2000;11:3699–702.CrossRefPubMedGoogle Scholar
  58. 58.
    Das I, Khan NS, Puri BK, Hirsch SR. Elevated endogenous nitric oxide synthase inhibitor in schizophrenic plasma may reflect abnormalities in brain nitric oxide production. Neurosci Lett. 1996;215:209–11.CrossRefPubMedGoogle Scholar
  59. 59.
    Dawson TM, Dawson VL. ADP-ribosylation as a mechanism for the action of nitric oxide in the nervous system. New Horiz. 1995;3:85–92.PubMedGoogle Scholar
  60. 60.
    Dawson TM, Sasaki M, Gonzalez-Zulueta M, Dawson VL. Regulation of neuronal nitric oxide synthase and identification of novel nitric oxide signaling pathways. Prog Brain Res. 1998;118:3–11.CrossRefPubMedGoogle Scholar
  61. 61.
    Dawson TM, Snyder SH. Gases as biological messengers: nitric oxide and carbon monoxide in the brain. J Neurosci. 1994;14:5147–59.PubMedGoogle Scholar
  62. 62.
    De Luca G, Di Giorgio RM, Macaione S, Calpona PR, Di Paola ED, Costa N, Cuzzocrea S, Citraro R, Russo E, De Sarro G. Amino acid levels in some brain areas of inducible nitric oxide synthase knock out mouse (iNOS−/−) before and after pentylenetetrazole kindling. Pharmacol Biochem Behav. 2006;85:804–12.CrossRefPubMedGoogle Scholar
  63. 63.
    de Vente J, Hopkins DA, Markerink-Van IM, Emson PC, Schmidt HH, Steinbusch HW. Distribution of nitric oxide synthase and nitric oxide-receptive, cyclic GMP-producing structures in the rat brain. Neuroscience. 1998;87:207–41.CrossRefPubMedGoogle Scholar
  64. 64.
    Denninger JW, Marletta MA. Guanylate cyclase and the NO/cGMP signaling pathway. Biochim Biophys Acta. 1999;1411:334–50.CrossRefPubMedGoogle Scholar
  65. 65.
    Dhir A, Kulkarni SK. Involvement of nitric oxide (NO) signaling pathway in the antidepressant action of bupropion, a dopamine reuptake inhibitor. Eur J Pharmacol. 2007;568:177–85.CrossRefPubMedGoogle Scholar
  66. 66.
    Ding JD, Burette A, Nedvetsky PI, Schmidt HH, Weinberg RJ. Distribution of soluble guanylyl cyclase in the rat brain. J Comp Neurol. 2004;472:437–48.CrossRefPubMedGoogle Scholar
  67. 67.
    Duman RS, Malberg J, Nakagawa S. Regulation of adult neurogenesis by psychotropic drugs and stress. J Pharmacol Exp Ther. 2001;299:401–7.PubMedGoogle Scholar
  68. 68.
    Duman RS, Nakagawa S, Malberg J. Regulation of adult neurogenesis by antidepressant treatment. Neuropsychopharmacology. 2001;25:836–44.CrossRefPubMedGoogle Scholar
  69. 69.
    Ehninger D, Kempermann G. Neurogenesis in the adult hippocampus. Cell Tissue Res. 2008;331:243–50.CrossRefPubMedGoogle Scholar
  70. 70.
    Ehringer H, Hornykiewicz O, Lechner K. Die Wirkung von Methylenblau auf die Monoaminoxydase und den Katecholamin-und 5-Hydroxytryptaminstoffwechsel des Gehirnes. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1961;241:568–82.CrossRefPubMedGoogle Scholar
  71. 71.
    Ergun Y, Ergun UG. Prevention of pro-depressant effect of L-arginine in the forced swim test by NG-nitro-L-arginine and [1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one]. Eur J Pharmacol. 2007;554:150–4.CrossRefPubMedGoogle Scholar
  72. 72.
    Eroglu L, Caglayan B. Anxiolytic and antidepressant properties of methylene blue in animal models. Pharmacol Res. 1997;36:381–5.CrossRefPubMedGoogle Scholar
  73. 73.
    Estall LB, Grant SJ, Cicala GA. Inhibition of nitric oxide (NO) production selectively impairs learning and memory in the rat. Pharmacol Biochem Behav. 1993;46:959–62.CrossRefPubMedGoogle Scholar
  74. 74.
    Ferreira FR, Oliveira AM, Dinarte AR, Pinheiro DG, Greene LJ, Silva Jr WA, Joca SR, Guimaraes FS. Changes in hippocampal gene expression by 7-nitroindazole in rats submitted to forced swimming stress. Genes Brain Behav. 2012;11:303–13.CrossRefPubMedGoogle Scholar
  75. 75.
    Feyissa AM, Chandran A, Stockmeier CA, Karolewicz B. Reduced levels of NR2A and NR2B subunits of NMDA receptor and PSD-95 in the prefrontal cortex in major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2008. doi: 10.1016/j.pnpbp.2008.10.005.PubMedCentralGoogle Scholar
  76. 76.
    Finkel MS, Laghrissi-Thode F, Pollock BG, Rong J. Paroxetine is a novel nitric oxide synthase inhibitor. Psychopharmacol Bull. 1996;32:653–8.PubMedGoogle Scholar
  77. 77.
    Florenzano F, Viscomi MT, Amadio S, D’Ambrosi N, Volonte C, Molinari M. Do ATP and NO interact in the CNS? Prog Neurobiol. 2008;84:40–56.CrossRefPubMedGoogle Scholar
  78. 78.
    Forstermann U, Gath I, Schwarz P, Closs EI, Kleinert H. Isoforms of nitric oxide synthase. Properties, cellular distribution and expressional control. Biochem Pharmacol. 1995;50:1321–32.CrossRefPubMedGoogle Scholar
  79. 79.
    Forstermann U, Schmidt HH, Pollock JS, Sheng H, Mitchell JA, Warner TD, Nakane M, Murad F. Isoforms of nitric oxide synthase. Characterization and purification from different cell types. Biochem Pharmacol. 1991;42:1849–57.CrossRefPubMedGoogle Scholar
  80. 80.
    Fossier P, Blanchard B, Ducrocq C, Leprince C, Tauc L, Baux G. Nitric oxide transforms serotonin into an inactive form and this affects neuromodulation. Neuroscience. 1999;93:597–603.CrossRefPubMedGoogle Scholar
  81. 81.
    Frey C, Narayanan K, McMillan K, Spack L, Gross SS, Masters BS, Griffith OW. L-thiocitrulline. A stereospecific, heme-binding inhibitor of nitric-oxide synthases. J Biol Chem. 1994;269:26083–91.PubMedGoogle Scholar
  82. 82.
    Gadek-Michalska A, Bugajski J. Nitric oxide in the adrenergic-and CRH-induced activation of hypothalamic-pituitary-adrenal axis. J Physiol Pharmacol. 2008;59:365–78.PubMedGoogle Scholar
  83. 83.
    Galecki P, Maes M, Florkowski A, Lewinski A, Galecka E, Bienkiewicz M, Szemraj J. Association between inducible and neuronal nitric oxide synthase polymorphisms and recurrent depressive disorder. J Affect Disord. 2011;129:175–82.CrossRefPubMedGoogle Scholar
  84. 84.
    Galimberti D, Scarpini E, Venturelli E, Strobel A, Herterich S, Fenoglio C, Guidi I, Scalabrini D, Cortini F, Bresolin N, Lesch KP, Reif A. Association of a NOS1 promoter repeat with Alzheimer’s disease. Neurobiol Aging. 2008;29:1359–65.CrossRefPubMedGoogle Scholar
  85. 85.
    Gardiner SM, Kemp PA, March JE, Bennett T. Influence of aminoguanidine and the endothelin antagonist, SB 209670, on the regional haemodynamic effects of endotoxaemia in conscious rats. Br J Pharmacol. 1996;118:1822–8.CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Garthwaite J, Boulton CL. Nitric oxide signaling in the central nervous system. Annu Rev Physiol. 1995;57:683–706.CrossRefPubMedGoogle Scholar
  87. 87.
    Garthwaite J, Charles SL, Chess-Williams R. Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain. Nature. 1988;336:385–8.CrossRefPubMedGoogle Scholar
  88. 88.
    Garthwaite J, Garthwaite G, Palmer RM, Moncada S. NMDA receptor activation induces nitric oxide synthesis from arginine in rat brain slices. Eur J Pharmacol. 1989;172:413–6.CrossRefPubMedGoogle Scholar
  89. 89.
    Gaston BM, Carver J, Doctor A, Palmer LA. S-nitrosylation signaling in cell biology. Mol Interv. 2003;3:253–63.CrossRefPubMedGoogle Scholar
  90. 90.
    Ghasemi M, Sadeghipour H, Mosleh A, Sadeghipour HR, Mani AR, Dehpour AR. Nitric oxide involvement in the antidepressant-like effects of acute lithium administration in the mouse forced swimming test. Eur Neuropsychopharmacol. 2008;18:323–32.CrossRefPubMedGoogle Scholar
  91. 91.
    Gilhotra N, Dhingra D. Involvement of NO-cGMP pathway in anti-anxiety effect of aminoguanidine in stressed mice. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33:1502–7.Google Scholar
  92. 92.
    Gillman PK. Methylene blue is a potent monoamine oxidase inhibitor. Can J Anaesth. 2008;55:311–2. author reply 312.CrossRefPubMedGoogle Scholar
  93. 93.
    Givalois L, Li S, Pelletier G. Central nitric oxide regulation of the hypothalamic-pituitary-adrenocortical axis in adult male rats. Mol Brain Res. 2002;102:1–8.CrossRefPubMedGoogle Scholar
  94. 94.
    Griffith OW, Kilbourn RG. Nitric oxide synthase inhibitors: amino acids. Methods Enzymol. 1996;268:375–92.CrossRefPubMedGoogle Scholar
  95. 95.
    Griffiths MJ, Messent M, Curzen NP, Evans TW. Aminoguanidine selectively decreases cyclic GMP levels produced by inducible nitric oxide synthase. Am J Respir Crit Care Med. 1995;152:1599–604.CrossRefPubMedGoogle Scholar
  96. 96.
    Griffiths MJ, Messent M, MacAllister RJ, Evans TW. Aminoguanidine selectively inhibits inducible nitric oxide synthase. Br J Pharmacol. 1993;110:963–8.CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Gustavsson A, Svensson M, Jacobi F, Allgulander C, Alonso J, Beghi E, Dodel R, Ekman M, Faravelli C, Fratiglioni L, Gannon B, Jones DH, Jennum P, Jordanova A, Jonsson L, Karampampa K, Knapp M, Kobelt G, Kurth T, Lieb R, Linde M, Ljungcrantz C, Maercker A, Melin B, Moscarelli M, Musayev A, Norwood F, Preisig M, Pugliatti M, Rehm J, Salvador-Carulla L, Schlehofer B, Simon R, Steinhausen HC, Stovner LJ, Vallat JM, Van den Bergh P, van Os J, Vos P, Xu W, Wittchen HU, Jonsson B, Olesen J, Group CD. Cost of disorders of the brain in Europe 2010. Eur Neuropsychopharmacol. 2011;21:718–79.CrossRefPubMedGoogle Scholar
  98. 98.
    Halaris A, Piletz JE. Imidazoline receptors: possible involvement in the pathophysiology and treatment of depression. Hum Psychopharmacol Clin Exp. 2001;16:65–9.CrossRefGoogle Scholar
  99. 99.
    Halaris A, Piletz JE. Relevance of imidazoline receptors and agmatine to psychiatry: a decade of progress. Ann N Y Acad Sci. 2003;1009:1–20.CrossRefPubMedGoogle Scholar
  100. 100.
    Halaris A, Zhu H, Feng Y, Piletz JE. Plasma agmatine and platelet imidazoline receptors in depression. Ann N Y Acad Sci. 1999;881:445–51.CrossRefPubMedGoogle Scholar
  101. 101.
    Handy RL, Harb HL, Wallace P, Gaffen Z, Whitehead KJ, Moore PK. Inhibition of nitric oxide synthase by 1-(2-trifluoromethylphenyl) imidazole (TRIM) in vitro: antinociceptive and cardiovascular effects. Br J Pharmacol. 1996;119:423–31.CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Handy RL, Moore PK. Mechanism of the inhibition of neuronal nitric oxide synthase by 1-(2- trifluoromethylphenyl) imidazole (TRIM). Life Sci. 1997;60:L389–94.CrossRefGoogle Scholar
  103. 103.
    Handy RL, Wallace P, Gaffen ZA, Whitehead KJ, Moore PK. The antinociceptive effect of 1-(2-trifluoromethylphenyl) imidazole (TRIM), a potent inhibitor of neuronal nitric oxide synthase in vitro, in the mouse. Br J Pharmacol. 1995;116:2349–50.CrossRefPubMedPubMedCentralGoogle Scholar
  104. 104.
    Hara H, Waeber C, Huang PL, Fujii M, Fishman MC, Moskowitz MA. Brain distribution of nitric oxide synthase in neuronal or endothelial nitric oxide synthase mutant mice using [3H]L-NG-nitro-arginine autoradiography. Neuroscience. 1996;75:881–90.CrossRefPubMedGoogle Scholar
  105. 105.
    Harkin A, Connor TJ, Burns MP, Kelly JP. Nitric oxide synthase inhibitors augment the effects of serotonin re-uptake inhibitors in the forced swimming test. Eur Neuropsychopharmacol. 2004;14:274–81.CrossRefPubMedGoogle Scholar
  106. 106.
    Harkin A, Connor TJ, Walsh M, St John N, Kelly JP. Serotonergic mediation of the antidepressant-like effects of nitric oxide synthase inhibitors. Neuropharmacology. 2003;44:616–23.CrossRefPubMedGoogle Scholar
  107. 107.
    Harkin AJ, Bruce KH, Craft B, Paul IA. Nitric oxide synthase inhibitors have antidepressant-like properties in mice. 1. Acute treatments are active in the forced swim test. Eur J Pharmacol. 1999;372:207–13.CrossRefPubMedGoogle Scholar
  108. 108.
    Harvey BH, Bothma T, Nel A, Wegener G, Stein DJ. Involvement of the NMDA receptor, NO-cyclic GMP and nuclear factor K-beta in an animal model of repeated trauma. Hum Psychopharmacol Clin Exp. 2005;20:367–73.CrossRefGoogle Scholar
  109. 109.
    Harvey BH, Oosthuizen F, Brand L, Wegener G, Stein DJ. Stress-restress evokes sustained iNOS activity and altered GABA levels and NMDA receptors in rat hippocampus. Psychopharmacology. 2004;175:494–502.CrossRefPubMedGoogle Scholar
  110. 110.
    Hasan K, Heesen BJ, Corbett JA, McDaniel ML, Chang K, Allison W, Wolffenbuttel BH, Williamson JR, Tilton RG. Inhibition of nitric oxide formation by guanidines. Eur J Pharmacol. 1993;249:101–6.CrossRefPubMedGoogle Scholar
  111. 111.
    Heiberg IL, Wegener G, Rosenberg R. Reduction of cGMP and nitric oxide has antidepressant-like effects in the forced swimming test in rats. Behav Brain Res. 2002;134:479–84.CrossRefPubMedGoogle Scholar
  112. 112.
    Herken H, Gurel A, Selek S, Armutcu F, Ozen ME, Bulut M, Kap O, Yumru M, Savas HA, Akyol O. Adenosine deaminase, nitric oxide, superoxide dismutase, and xanthine oxidase in patients with major depression: impact of antidepressant treatment. Arch Med Res. 2007;38:247–52.CrossRefPubMedGoogle Scholar
  113. 113.
    Herrera-Guzman I, Gudayol-Ferre E, Herrera-Guzman D, Guardia-Olmos J, Hinojosa-Calvo E, Herrera-Abarca JE. Effects of selective serotonin reuptake and dual serotonergic-noradrenergic reuptake treatments on memory and mental processing speed in patients with major depressive disorder. J Psychiatr Res. 2009;43:855–63.CrossRefPubMedGoogle Scholar
  114. 114.
    Herzberg L, Herzberg B. Mood change and magnesium. A possible interaction between magnesium and lithium? J Nerv Ment Dis. 1977;165:423–6.CrossRefPubMedGoogle Scholar
  115. 115.
    Hess DT, Patterson SI, Smith DS, Skene JH. Neuronal growth cone collapse and inhibition of protein fatty acylation by nitric oxide. Nature. 1993;366:562–5.CrossRefPubMedGoogle Scholar
  116. 116.
    Hibbs Jr JB, Taintor RR, Vavrin Z. Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite. Science. 1987;235:473–6.CrossRefPubMedGoogle Scholar
  117. 117.
    Hindley S, Juurlink BH, Gysbers JW, Middlemiss PJ, Herman MA, Rathbone MP. Nitric oxide donors enhance neurotrophin-induced neurite outgrowth through a cGMP-dependent mechanism. J Neurosci Res. 1997;47:427–39.CrossRefPubMedGoogle Scholar
  118. 118.
    Hiroaki-Sato VA, Sales AJ, Biojone C, Joca SR. Hippocampal nNOS inhibition induces an antidepressant-like effect: involvement of 5HT1A receptors. Behav Pharmacol. 2014;25:187–96.CrossRefPubMedGoogle Scholar
  119. 119.
    Hojgaard Rasmussen H, Bo Mortensen P, Jensen IW. Depression and magnesium deficiency. Int J Psychiatry Med. 1989;19:57–63.CrossRefGoogle Scholar
  120. 120.
    Holderbach R, Clark K, Moreau JL, Bischofberger J, Normann C. Enhanced long-term synaptic depression in an animal model of depression. Biol Psychiatry. 2007;62:92–100.CrossRefPubMedGoogle Scholar
  121. 121.
    Holscher C. 7-Nitro indazole, a neuron-specific nitric oxide synthase inhibitor, produces amnesia in the chick. Learn Mem. 1994;1:213–6.PubMedGoogle Scholar
  122. 122.
    Holscher C, McGlinchey L, Anwyl R, Rowan MJ. 7-Nitro indazole, a selective neuronal nitric oxide synthase inhibitor in vivo, impairs spatial learning in the rat. Learn Mem. 1996;2:267–78.CrossRefPubMedGoogle Scholar
  123. 123.
    Holstad M, Jansson L, Sandler S. Effects of aminoguanidine on rat pancreatic islets in culture and on the pancreatic islet blood flow of anaesthetized rats. Biochem Pharmacol. 1996;51:1711–7.CrossRefPubMedGoogle Scholar
  124. 124.
    Hua Y, Huang XY, Zhou L, Zhou QG, Hu Y, Luo CX, Li F, Zhu DY. DETA/NONOate, a nitric oxide donor, produces antidepressant effects by promoting hippocampal neurogenesis. Psychopharmacology. 2008;200:231–42.CrossRefPubMedGoogle Scholar
  125. 125.
    Inan SY, Yalcin I, Aksu F. Dual effects of nitric oxide in the mouse forced swimming test: possible contribution of nitric oxide-mediated serotonin release and potassium channel modulation. Pharmacol Biochem Behav. 2004;77:457–64.CrossRefPubMedGoogle Scholar
  126. 126.
    Ishibashi Y, Shimada T, Murakami Y, Takahashi N, Sakane T, Sugamori T, Ohata S, Inoue S, Ohta Y, Nakamura K, Shimizu H, Katoh H, Hashimoto M. An inhibitor of inducible nitric oxide synthase decreases forearm blood flow in patients with congestive heart failure. J Am Coll Cardiol. 2001;38:1470–6.CrossRefPubMedGoogle Scholar
  127. 127.
    Jakubovic A, Necina J. The effect of methylene blue on the monoamine oxidase activity of the liver and brain of rats after various routes of administration. Arzneimittelforschung. 1963;13:134–6.PubMedGoogle Scholar
  128. 128.
    Jankord R, McAllister RM, Ganjam VK, Laughlin MH. Chronic inhibition of nitric oxide synthase augments the ACTH response to exercise. Am J Physiol Regul Integr Comp Physiol. 2009;296:R728–34.CrossRefPubMedPubMedCentralGoogle Scholar
  129. 129.
    Jefferys D, Funder J. Nitric oxide modulates retention of immobility in the forced swimming test in rats. Eur J Pharmacol. 1996;295:131–5.CrossRefPubMedGoogle Scholar
  130. 130.
    Jesse CR, Bortolatto CF, Savegnago L, Rocha JB, Nogueira CW. Involvement of L-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of tramadol in the rat forced swimming test. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32:1838–43.CrossRefPubMedGoogle Scholar
  131. 131.
    Joca S, Stanquini L, Ferreira F, Guimaraes F. Chronic, but not acute, inhibition of nitric oxide (NO) synthesis prevents learned helplessness development in rats. Int J Neuropsychopharmacol. 2008;11:122–122.Google Scholar
  132. 132.
    Joca SR, Guimaraes FS. Inhibition of neuronal nitric oxide synthase in the rat hippocampus induces antidepressant-like effects. Psychopharmacology (Berl). 2006;185:298–305.CrossRefGoogle Scholar
  133. 133.
    Johnson MD, Ma PM. Localization of NADPH diaphorase activity in monoaminergic neurons of the rat brain. J Comp Neurol. 1993;332:391–406.CrossRefPubMedGoogle Scholar
  134. 134.
    Juch M, Smalla KH, Kahne T, Lubec G, Tischmeyer W, Gundelfinger ED, Engelmann M. Congenital lack of nNOS impairs long-term social recognition memory and alters the olfactory bulb proteome. Neurobiol Learn Mem. 2009;92:469–84.CrossRefPubMedGoogle Scholar
  135. 135.
    Kaehler ST, Singewald N, Sinner C, Philippu A. Nitric oxide modulates the release of serotonin in the rat hypothalamus. Brain Res. 1999;835:346–9.CrossRefPubMedGoogle Scholar
  136. 136.
    Karolewicz B, Paul IA, Antkiewicz-Michaluk L. Effect of NOS inhibitor on forced swim test and neurotransmitters turnover in the mouse brain. Pol J Pharmacol. 2001;53:587–96.PubMedGoogle Scholar
  137. 137.
    Karolewicz B, Szebeni K, Stockmeier CA, Konick L, Overholser JC, Jurjus G, Roth BL, Ordway GA. Low nNOS protein in the locus coeruleus in major depression. J Neurochem. 2004;91:1057–66.CrossRefPubMedPubMedCentralGoogle Scholar
  138. 138.
    Kendler KS, Thornton LM, Gardner CO. Stressful life events and previous episodes in the etiology of major depression in women: an evaluation of the ‘kindling’ hypothesis. Am J Psychiatry. 2000;157:1243–51.CrossRefPubMedGoogle Scholar
  139. 139.
    Kerwin Jr JF, Heller M. The arginine-nitric oxide pathway: a target for new drugs. Med Res Rev. 1994;14:23–74.CrossRefPubMedGoogle Scholar
  140. 140.
    Kim YK, Paik JW, Lee SW, Yoon D, Han C, Lee BH. Increased plasma nitric oxide level associated with suicide attempt in depressive patients. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30:1091–6.CrossRefPubMedGoogle Scholar
  141. 141.
    Kiss JP, Vizi ES. Nitric oxide: a novel link between synaptic and nonsynaptic transmission. Trends Neurosci. 2001;24:211–5.Google Scholar
  142. 142.
    Knott AB, Bossy-Wetzel E. Nitric oxide in health and disease of the nervous system. Antioxid Redox Signal. 2009;11:541–53.Google Scholar
  143. 143.
    Knowles RG, Moncada S. Nitric oxide synthases in mammals. Biochem J. 1994;298(Pt 2):249–58.CrossRefPubMedPubMedCentralGoogle Scholar
  144. 144.
    Kowall NW, Ferrante RJ, Beal MF, Richardson Jr EP, Sofroniew MV, Cuello AC, Martin JB. Neuropeptide Y, somatostatin, and reduced nicotinamide adenine dinucleotide phosphate diaphorase in the human striatum: a combined immunocytochemical and enzyme histochemical study. Neuroscience. 1987;20:817–28.CrossRefPubMedGoogle Scholar
  145. 145.
    Krass M, Wegener G, Vasar E, Volke V. Antidepressant-like effect of agmatine is not mediated by serotonin. Behav Brain Res. 2008;188:324–8.CrossRefPubMedGoogle Scholar
  146. 146.
    Kuhn DM, Arthur Jr R. Molecular mechanism of the inactivation of tryptophan hydroxylase by nitric oxide: attack on critical sulfhydryls that spare the enzyme iron center. J Neurosci. 1997;17:7245–51.PubMedGoogle Scholar
  147. 147.
    Kuhn DM, Arthur Jr RE. Inactivation of brain tryptophan hydroxylase by nitric oxide. J Neurochem. 1996;67:1072–7.CrossRefPubMedGoogle Scholar
  148. 148.
    Kurt M, Bilge SS, Aksoz E, Kukula O, Celik S, Kesim Y. Effect of sildenafil on anxiety in the plus-maze test in mice. Pol J Pharmacol. 2004;56:353–7.PubMedGoogle Scholar
  149. 149.
    Laitinen JT, Laitinen KS, Tuomisto L, Airaksinen MM. Differential regulation of cyclic GMP levels in the frontal cortex and the cerebellum of anesthetized rats by nitric oxide: an in vivo microdialysis study. Brain Res. 1994;668:117–21.CrossRefPubMedGoogle Scholar
  150. 150.
    Lassen LH, Ashina M, Christiansen I, Ulrich V, Grover R, Donaldson J, Olesen J. Nitric oxide synthase inhibition: a new principle in the treatment of migraine attacks. Cephalgia. 1998;18:27–32.CrossRefGoogle Scholar
  151. 151.
    Lassen LH, Ashina M, Christiansen I, Ulrich V, Olesen J. Nitric oxide synthase inhibition in migraine [letter]. Lancet. 1997;349:401–2.CrossRefPubMedGoogle Scholar
  152. 152.
    Lee BH, Lee SW, Yoon D, Lee HJ, Yang JC, Shim SH, Kim DH, Ryu SH, Han C, Kim YK. Increased plasma nitric oxide metabolites in suicide attempters. Neuropsychobiology. 2006;53:127–32.CrossRefPubMedGoogle Scholar
  153. 153.
    Lemaire JF, McPherson PS. Binding of Vac14 to neuronal nitric oxide synthase: characterisation of a new internal PDZ-recognition motif. FEBS Lett. 2006;580:6948–54.CrossRefPubMedGoogle Scholar
  154. 154.
    Li G, Regunathan S, Barrow CJ, Eshraghi J, Cooper R, Reis DJ. Agmatine: an endogenous clonidine-displacing substance in the brain. Science. 1994;263:966–9.CrossRefPubMedGoogle Scholar
  155. 155.
    Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M, Li XY, Aghajanian G, Duman RS. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science. 2010;329:959–64.CrossRefPubMedPubMedCentralGoogle Scholar
  156. 156.
    Li YF, Gong ZH, Cao JB, Wang HL, Luo ZP, Li J. Antidepressant-like effect of agmatine and its possible mechanism. Eur J Pharmacol. 2003;469:81–8.CrossRefPubMedGoogle Scholar
  157. 157.
    Liebenberg N, Joca S, Wegener G. Nitric oxide involvement in the antidepressant-like effect of ketamine in the Flinders sensitive line rat model of depression. Acta Neuropsychiatr. 2015;27(2):90–6.Google Scholar
  158. 158.
    Linden DJ, Dawson TM, Dawson VL. An evaluation of the nitric oxide/cGMP/cGMP-dependent protein kinase cascade in the induction of cerebellar long-term depression in culture. J Neurosci. 1995;15:5098–105.PubMedGoogle Scholar
  159. 159.
    Lonart G, Cassels KL, Johnson KM. Nitric oxide induces calcium-dependent [3H]dopamine release from striatal slices. J Neurosci Res. 1993;35:192–8.CrossRefPubMedGoogle Scholar
  160. 160.
    Lonart G, Johnson KM. Inhibitory effects of nitric oxide on the uptake of [3H]dopamine and [3H]glutamate by striatal synaptosomes. J Neurochem. 1994;63:2108–17.CrossRefPubMedGoogle Scholar
  161. 161.
    Lorrain DS, Hull EM. Nitric oxide increases dopamine and serotonin release in the medial preoptic area. Neuroreport. 1993;5:87–9.CrossRefPubMedGoogle Scholar
  162. 162.
    Lowenstein CJ, Snyder SH. Nitric oxide, a novel biologic messenger. Cell. 1992;70:705–7.CrossRefPubMedGoogle Scholar
  163. 163.
    Lowy MT, Wittenberg L, Yamamoto BK. Effect of acute stress on hippocampal glutamate levels and spectrin proteolysis in young and aged rats. J Neurochem. 1995;65:268–74.CrossRefPubMedGoogle Scholar
  164. 164.
    Luo D, Vincent SR. NMDA-dependent nitric oxide release in the hippocampus in vivo: interactions with noradrenaline. Neuropharmacology. 1994;33:1345–50.CrossRefPubMedGoogle Scholar
  165. 165.
    Machado-Vieira R, Salvadore G, Diazgranados N, Zarate Jr CA. Ketamine and the next generation of antidepressants with a rapid onset of action. Pharmacol Ther. 2009;123:143–50.CrossRefPubMedPubMedCentralGoogle Scholar
  166. 166.
    Madison DV, Malenka RC, Nicoll RA. Mechanisms underlying long-term potentiation of synaptic transmission. Annu Rev Neurosci. 1991;14:379–97.CrossRefPubMedGoogle Scholar
  167. 167.
    Madrigal JL, Moro MA, Lizasoain I, Lorenzo P, Castrillo A, Bosca L, Leza JC. Inducible nitric oxide synthase expression in brain cortex after acute restraint stress is regulated by nuclear factor kappaB-mediated mechanisms. J Neurochem. 2001;76:532–8.CrossRefPubMedGoogle Scholar
  168. 168.
    Madrigal JLM, Moro MA, Lizasoain I, Lorenzo P, Leza JC. Stress-induced increase in extracellular sucrose space in rats is mediated by nitric oxide. Brain Res. 2002;938:87–91.CrossRefPubMedGoogle Scholar
  169. 169.
    Maeng S, Zarate Jr CA. The role of glutamate in mood disorders: results from the ketamine in major depression study and the presumed cellular mechanism underlying its antidepressant effects. Curr Psychiatry Rep. 2007;9:467–74.CrossRefPubMedGoogle Scholar
  170. 170.
    Malenka RC. Synaptic plasticity in the hippocampus: LTP and LTD. Cell. 1994;78:535–8.CrossRefPubMedGoogle Scholar
  171. 171.
    Marletta MA. Nitric oxide synthase structure and mechanism. J Biol Chem. 1993;268:12231–4.PubMedGoogle Scholar
  172. 172.
    Matarredona ER, Murillo-Carretero M, Moreno-López B, Estrada C. Nitric oxide synthesis inhibition increases proliferation of neural precursors isolated from the postnatal mouse subventricular zone. Brain Res. 2004;995:274–84.CrossRefPubMedGoogle Scholar
  173. 173.
    Mayer B, Brunner F, Schmidt K. Inhibition of nitric oxide synthesis by methylene blue. Biochem Pharmacol. 1993;45:367–74.CrossRefPubMedGoogle Scholar
  174. 174.
    Mayer B, Brunner F, Schmidt K. Novel actions of methylene blue. Eur Heart J. 1993;14(Suppl I):22–6.PubMedGoogle Scholar
  175. 175.
    Mayer B, Klatt P, Werner ER, Schmidt K. Molecular mechanisms of inhibition of porcine brain nitric oxide synthase by the antinociceptive drug 7-nitro-indazole [published erratum appears in Neuropharmacology 1995 Feb;34(2):243]. Neuropharmacology. 1994;33:1253–9.CrossRefPubMedGoogle Scholar
  176. 176.
    Meffert MK, Calakos NC, Scheller RH, Schulman H. Nitric oxide modulates synaptic vesicle docking fusion reactions. Neuron. 1996;16:1229–36.CrossRefPubMedGoogle Scholar
  177. 177.
    Meffert MK, Premack BA, Schulman H. Nitric oxide stimulates Ca(2+)-independent synaptic vesicle release. Neuron. 1994;12:1235–44.CrossRefPubMedGoogle Scholar
  178. 178.
    Michael-Titus AT, Bains S, Jeetle J, Whelpton R. Imipramine and phenelzine decrease glutamate overflow in the prefrontal cortex – a possible mechanism of neuroprotection in major depression? Neuroscience. 2000;100:681–4.CrossRefPubMedGoogle Scholar
  179. 179.
    Miki N, Kawabe Y, Kuriyama K. Activation of cerebral guanylate cyclase by nitric oxide. Biochem Biophys Res Commun. 1977;75:851–6.CrossRefPubMedGoogle Scholar
  180. 180.
    Mizuno M, Yamada K, Olariu A, Nawa H, Nabeshima T. Involvement of brain-derived neurotrophic factor in spatial memory formation and maintenance in a radial arm maze test in rats. J Neurosci. 2000;20:7116–21.PubMedGoogle Scholar
  181. 181.
    Mogensen J, Wortwein G, Gustafson B, Ermens P. L-nitroarginine reduces hippocampal mediation of place learning in the rat. Neurobiol Learn Mem. 1995;64:17–24.CrossRefPubMedGoogle Scholar
  182. 182.
    Mogensen J, Wortwein G, Hasman A, Nielsen P, Wang Q. Functional and neurochemical profile of place learning after L-nitro-arginine in the rat. Neurobiol Learn Mem. 1995;63:54–65.CrossRefPubMedGoogle Scholar
  183. 183.
    Moncada S, Palmer RM, Higgs EA. Biosynthesis of nitric oxide from L-arginine. A pathway for the regulation of cell function and communication. Biochem Pharmacol. 1989;38:1709–15.CrossRefPubMedGoogle Scholar
  184. 184.
    Montezuma K, Biojone C, Lisboa SF, Cunha FQ, Guimaraes FS, Joca SR. Inhibition of iNOS induces antidepressant-like effects in mice: pharmacological and genetic evidence. Neuropharmacology. 2012;62:485–91.CrossRefPubMedGoogle Scholar
  185. 185.
    Moore PK, Babbedge RC, Wallace P, Gaffen ZA, Hart SL. 7-Nitro indazole, an inhibitor of nitric oxide synthase, exhibits anti-nociceptive activity in the mouse without increasing blood pressure. Br J Pharmacol. 1993;108:296–7.CrossRefPubMedPubMedCentralGoogle Scholar
  186. 186.
    Mori K, Togashi H, Ueno KI, Matsumoto M, Yoshioka M. Aminoguanidine prevented the impairment of learning behavior and hippocampal long-term potentiation following transient cerebral ischemia. Behav Brain Res. 2001;120:159–68.CrossRefPubMedGoogle Scholar
  187. 187.
    Mungrue IN, Bredt DS. nNOS at a glance: implications for brain and brawn. J Cell Sci. 2004;117:2627–9.CrossRefPubMedGoogle Scholar
  188. 188.
    Murad F, Mittal CK, Arnold WP, Katsuki S, Kimura H. Guanylate cyclase: activation by azide, nitro compounds, nitric oxide, and hydroxyl radical and inhibition by hemoglobin and myoglobin. Adv Cyclic Nucleotide Res. 1978;9:145–58.PubMedGoogle Scholar
  189. 189.
    Murck H. Magnesium and affective disorders. Nutr Neurosci. 2002;5:375–89.CrossRefPubMedGoogle Scholar
  190. 190.
    Musazzi L, Milanese M, Farisello P, Zappettini S, Tardito D, Barbiero VS, Bonifacino T, Mallei A, Baldelli P, Racagni G, Raiteri M, Benfenati F, Bonanno G, Popoli M. Acute stress increases depolarization-evoked glutamate release in the rat prefrontal/frontal cortex: the dampening action of antidepressants. PLoS One. 2010;5:e8566.CrossRefPubMedPubMedCentralGoogle Scholar
  191. 191.
    Narsapur SL, Naylor GJ. Methylene blue. A possible treatment for manic depressive psychosis. J Affect Disord. 1983;5:155–61.CrossRefPubMedGoogle Scholar
  192. 192.
    Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J. 1992;6:3051–64.PubMedGoogle Scholar
  193. 193.
    Nathan C, Xie QW. Regulation of biosynthesis of nitric oxide. J Biol Chem. 1994;269:13725–8.PubMedGoogle Scholar
  194. 194.
    Naudon L, Hotte M, Jay TM. Effects of acute and chronic antidepressant treatments on memory performance: a comparison between paroxetine and imipramine. Psychopharmacology (Berl). 2007;191:353–64.CrossRefGoogle Scholar
  195. 195.
    Naylor GG, Smith AH. Reduction of vanadate, a possible explanation of the effect of phenothiazines in manic-depressive psychosis. Lancet. 1982;1:395–6.CrossRefPubMedGoogle Scholar
  196. 196.
    Naylor GJ. Vanadium and manic depressive psychosis. Nutr Health. 1984;3:79–85.CrossRefPubMedGoogle Scholar
  197. 197.
    Naylor GJ, Dick DA, Johnston BB, Hopwood SE, Dick EG, Smith AH, Kay D. Possible explanation for therapeutic action of lithium, and a possible substitute (methylene-blue) [letter]. Lancet. 1981;2:1175–6.CrossRefPubMedGoogle Scholar
  198. 198.
    Naylor GJ, Martin B, Hopwood SE, Watson Y. A two-year double-blind crossover trial of the prophylactic effect of methylene blue in manic-depressive psychosis. Biol Psychiatry. 1986;21:915–20.CrossRefPubMedGoogle Scholar
  199. 199.
    Naylor GJ, Smith AH, Connelly P. A controlled trial of methylene blue in severe depressive illness. Biol Psychiatry. 1987;22:657–9.CrossRefPubMedGoogle Scholar
  200. 200.
    Naylor GJ, Smith AH, Connelly P. Methylene blue in mania [letter]. Biol Psychiatry. 1988;24:941–2.CrossRefPubMedGoogle Scholar
  201. 201.
    Nelson RJ. Effects of nitric oxide on the HPA axis and aggression. Novartis Found Symp. 2005;268:147.CrossRefPubMedGoogle Scholar
  202. 202.
    Nelson RJ, Demas GE, Huang PL, Fishman MC, Dawson VL, Dawson TM, Snyder SH. Behavioural abnormalities in male mice lacking neuronal nitric oxide synthase. Nature. 1995;378:383–6.CrossRefPubMedGoogle Scholar
  203. 203.
    Nelson RJ, Trainor BC, Chiavegatto S, Demas GE. Pleiotropic contributions of nitric oxide to aggressive behavior. Neurosci Biobehav Rev. 2006;30:346–55.CrossRefPubMedGoogle Scholar
  204. 204.
    Normann C, Schmitz D, Furmaier A, Doing C, Bach M. Long-term plasticity of visually evoked potentials in humans is altered in major depression. Biol Psychiatry. 2007;62:373–80.CrossRefPubMedGoogle Scholar
  205. 205.
    Nudmamud-Thanoi S, Reynolds GP. The NR1 subunit of the glutamate/NMDA receptor in the superior temporal cortex in schizophrenia and affective disorders. Neurosci Lett. 2004;372:173–7.CrossRefPubMedGoogle Scholar
  206. 206.
    Nylén A, Skagerberg G, Alm P, Larsson B, Holmqvist B, Andersson KE. Nitric oxide synthase in the hypothalamic paraventricular nucleus of the female rat; organization of spinal projections and coexistence with oxytocin or vasopressin. Brain Res. 2001;908:10–24.CrossRefPubMedGoogle Scholar
  207. 207.
    O’Dell TJ, Hawkins RD, Kandel ER, Arancio O. Tests of the roles of two diffusible substances in long-term potentiation: evidence for nitric oxide as a possible early retrograde messenger. Proc Natl Acad Sci U S A. 1991;88:11285–9.CrossRefPubMedPubMedCentralGoogle Scholar
  208. 208.
    O’Dell TJ, Huang PL, Dawson TM, Dinerman JL, Snyder SH, Kandel ER, Fishman MC. Endothelial NOS and the blockade of LTP by NOS inhibitors in mice lacking neuronal NOS. Science. 1994;265:542–6.CrossRefPubMedGoogle Scholar
  209. 209.
    Ogawa T, Kimoto M, Watanabe H, Sasaoka K. Metabolism of NG, NG-and NG, N’G-dimethylarginine in rats. Arch Biochem Biophys. 1987;252:526–37.CrossRefPubMedGoogle Scholar
  210. 210.
    Ohno M, Yamamoto T, Watanabe S. Deficits in working memory following inhibition of hippocampal nitric oxide synthesis in the rat. Brain Res. 1993;632:36–40.CrossRefPubMedGoogle Scholar
  211. 211.
    Ohno M, Yamamoto T, Watanabe S. Intrahippocampal administration of the NO synthase inhibitor L-NAME prevents working memory deficits in rats exposed to transient cerebral ischemia. Brain Res. 1994;634:173–7.CrossRefPubMedGoogle Scholar
  212. 212.
    Okada D, Yap CC, Kojima H, Kikuchi K, Nagano T. Distinct glutamate receptors govern differential levels of nitric oxide production in a layer-specific manner in the rat cerebellar cortex. Neuroscience. 2004;125:461–72.CrossRefPubMedGoogle Scholar
  213. 213.
    Okumura T, Kishi T, Okochi T, Ikeda M, Kitajima T, Yamanouchi Y, Kinoshita Y, Kawashima K, Tsunoka T, Inada T, Ozaki N, Iwata N. Genetic association analysis of functional polymorphisms in neuronal nitric oxide synthase 1 gene (NOS1) and mood disorders and fluvoxamine response in major depressive disorder in the Japanese population. Neuropsychobiology. 2010;61:57–63.CrossRefPubMedGoogle Scholar
  214. 214.
    Olesen J, Gustavsson A, Svensson M, Wittchen HU, Jonsson B, Group Cs, European Brain C. The economic cost of brain disorders in Europe. Eur J Neurol. 2012;19:155–62.CrossRefPubMedGoogle Scholar
  215. 215.
    Olesen J, Leonardi M. The burden of brain diseases in Europe. Eur J Neurol. 2003;10:471–7.CrossRefPubMedGoogle Scholar
  216. 216.
    Olesen J, Sobscki P, Truelsen T, Sestoft D, Jonsson B. Cost of disorders of the brain in Denmark. Nord J Psychiatry. 2008;62:114–20.CrossRefPubMedGoogle Scholar
  217. 217.
    Oliveira RM, Guimaraes FS, Deakin JF. Expression of neuronal nitric oxide synthase in the hippocampal formation in affective disorders. Braz J Med Biol Res. 2008;41:333–41.CrossRefPubMedGoogle Scholar
  218. 218.
    Olivenza R, Moro MA, Lizasoain I, Lorenzo P, Fernández AP, Rodrigo J, Boscá L, Leza JC. Chronic stress induces the expression of inducible nitric oxide synthase in rat brain cortex. J Neurochem. 2000;74:785–91.CrossRefPubMedGoogle Scholar
  219. 219.
    Olmos G, DeGregorio-Rocasolano N, Paz Regalado M, Gasull T, Assumpcio Boronat M, Trullas R, Villarroel A, Lerma J, Garcia-Sevilla JA. Protection by imidazol(ine) drugs and agmatine of glutamate-induced neurotoxicity in cultured cerebellar granule cells through blockade of NMDA receptor. Br J Pharmacol. 1999;127:1317–26.CrossRefPubMedPubMedCentralGoogle Scholar
  220. 220.
    Oosthuizen F, Wegener G, Harvey BH. Nitric oxide as inflammatory mediator in post-traumatic stress disorder (PTSD): evidence from an animal model. Neuropsychiat Dis Treat. 2005;1:109–23.CrossRefGoogle Scholar
  221. 221.
    Orlando GF, Langnaese K, Schulz C, Wolf G, Engelmann M. Neuronal nitric oxide synthase gene inactivation reduces the expression of vasopressin in the hypothalamic paraventricular nucleus and of catecholamine biosynthetic enzymes in the adrenal gland of the mouse. Stress. 2008;11:42–51.CrossRefPubMedGoogle Scholar
  222. 222.
    Pacher P, Beckman JS, Liaudet L. Nitric oxide and peroxynitrite in health and disease. Physiol Rev. 2007;87:315–424.CrossRefPubMedPubMedCentralGoogle Scholar
  223. 223.
    Packer MA, Stasiv Y, Benraiss A, Chmielnicki E, Grinberg A, Westphal H, Goldman SA, Enikolopov G. Nitric oxide negatively regulates mammalian adult neurogenesis. Proc Natl Acad Sci U S A. 2003;100:9566–71.CrossRefPubMedPubMedCentralGoogle Scholar
  224. 224.
    Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987;327:524–6.CrossRefPubMedGoogle Scholar
  225. 225.
    Papa M, Pellicano MP, Sadile AG. Nitric oxide and long-term habituation to novelty in the rat. Ann N Y Acad Sci. 1994;738:316–24.CrossRefPubMedGoogle Scholar
  226. 226.
    Pavlinac D, Langer R, Lenhard L, Deftos L. Magnesium in affective disorders. Biol Psychiatry. 1979;14:657–61.PubMedGoogle Scholar
  227. 227.
    Pereira VS, Casarotto PC, Hiroaki-Sato VA, Sartim AG, Guimaraes FS, Joca SR. Antidepressant- and anticompulsive-like effects of purinergic receptor blockade: involvement of nitric oxide. Eur Neuropsychopharmacol. 2013;23:1769–78.CrossRefPubMedGoogle Scholar
  228. 228.
    Pinnock SB, Herbert J. Brain-derived neurotropic factor and neurogenesis in the adult rat dentate gyrus: interactions with corticosterone. Eur J Neurosci. 2008;27:2493–500.CrossRefPubMedPubMedCentralGoogle Scholar
  229. 229.
    Plech A, Klimkiewicz T, Maksym B. Effect of L-arginine on memory in rats. Pol J Pharmacol. 2003;55:987–92.CrossRefPubMedGoogle Scholar
  230. 230.
    Pogun S, Baumann MH, Kuhar MJ. Nitric oxide inhibits [3H]dopamine uptake. Brain Res. 1994;641:83–91.CrossRefPubMedGoogle Scholar
  231. 231.
    Pogun S, Dawson V, Kuhar MJ. Nitric oxide inhibits 3H-glutamate transport in synaptosomes. Synapse. 1994;18:21–6.CrossRefPubMedGoogle Scholar
  232. 232.
    Pogun S, Kuhar MJ. Regulation of neurotransmitter reuptake by nitric oxide. Ann N Y Acad Sci. 1994;738(305–15):305–15.PubMedGoogle Scholar
  233. 233.
    Poleszak E, Wlaź P, Kedzierska E, Nieoczym D, Wróbel A, Fidecka S, Pilc A, Nowak G. NMDA/glutamate mechanism of antidepressant-like action of magnesium in forced swim test in mice. Pharmacol Biochem Behav. 2007;88:158–64.CrossRefPubMedGoogle Scholar
  234. 234.
    Prast H, Philippu A. Nitric oxide as modulator of neuronal function. Prog Neurobiol. 2001;64:51–68.CrossRefPubMedGoogle Scholar
  235. 235.
    Radi R, Beckman JS, Bush KM, Freeman BA. Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. Arch Biochem Biophys. 1991;288:481–7.CrossRefPubMedGoogle Scholar
  236. 236.
    Radi R, Rubbo H. Antioxidant properties of nitric oxide. In: Cardenas E, Packer L, editors. Handbook of antioxidants. New York: CRC Press; 2001. p. 689–706.Google Scholar
  237. 237.
    Regunathan S, Reis DJ. Imidazoline receptors and their endogenous ligands. Annu Rev Pharmacol Toxicol. 1996;36:511–44.CrossRefPubMedGoogle Scholar
  238. 238.
    Reif A, Herterich S, Strobel A, Ehlis AC, Saur D, Jacob CP, Wienker T, Topner T, Fritzen S, Walter U, Schmitt A, Fallgatter AJ, Lesch KP. A neuronal nitric oxide synthase (NOS-I) haplotype associated with schizophrenia modifies prefrontal cortex function. Mol Psychiatry. 2006;11:286–300.CrossRefPubMedGoogle Scholar
  239. 239.
    Reif A, Jacob CP, Rujescu D, Herterich S, Lang S, Gutknecht L, Baehne CG, Strobel A, Freitag CM, Giegling I, Romanos M, Hartmann A, Rosler M, Renner TJ, Fallgatter AJ, Retz W, Ehlis AC, Lesch KP. Influence of functional variant of neuronal nitric oxide synthase on impulsive behaviors in humans. Arch Gen Psychiatry. 2009;66:41–50.CrossRefPubMedGoogle Scholar
  240. 240.
    Reif A, Strobel A, Jacob CP, Herterich S, Freitag CM, Topner T, Mossner R, Fritzen S, Schmitt A, Lesch KP. A NOS-III haplotype that includes functional polymorphisms is associated with bipolar disorder. Int J Neuropsychopharmacol. 2006;9:13–20.CrossRefPubMedGoogle Scholar
  241. 241.
    Rengasamy A, Johns RA. Regulation of nitric oxide synthase by nitric oxide. Mol Pharmacol. 1993;44:124–8.PubMedGoogle Scholar
  242. 242.
    Reznikov LR, Grillo CA, Piroli GG, Pasumarthi RK, Reagan LP, Fadel J. Acute stress-mediated increases in extracellular glutamate levels in the rat amygdala: differential effects of antidepressant treatment. Eur J Neurosci. 2007;25:3109–14.CrossRefPubMedGoogle Scholar
  243. 243.
    Riefler GM, Firestein BL. Binding of neuronal nitric-oxide synthase (nNOS) to carboxyl-terminal-binding protein (CtBP) changes the localization of ctbp from the nucleus to the cytosol: a novel function for targeting by the PDZ domain of nNOS. J Biol Chem. 2001;276:48262–8.PubMedGoogle Scholar
  244. 244.
    Rivier C, Shen GH. In the rat, endogenous nitric oxide modulates the response of the hypothalamic-pituitary-adrenal axis to interleukin-1β, vasopressin, and oxytocin. J Neurosci. 1994;14:1985–93.PubMedGoogle Scholar
  245. 245.
    Romero-Grimaldi C, Moreno-López B, Estrada C. Age-dependent effect of nitric oxide on subventricular zone and olfactory bulb neural precursor proliferation. J Comp Neurol. 2008;506:339–46.CrossRefPubMedGoogle Scholar
  246. 246.
    Rubbo H, Radi R, Trujillo M, Telleri R, Kalyanaraman B, Barnes S, Kirk M, Freeman BA. Nitric oxide regulation of superoxide and peroxynitrite-dependent lipid peroxidation. Formation of novel nitrogen-containing oxidized lipid derivatives. J Biol Chem. 1994;269:26066–75.PubMedGoogle Scholar
  247. 247.
    Rydgren T, Sandler S. Efficacy of 1400 W, a novel inhibitor of inducible nitric oxide synthase, in preventing interleukin-1beta-induced suppression of pancreatic islet function in vitro and multiple low-dose streptozotocin-induced diabetes in vivo. Eur J Endocrinol. 2002;147:543–51.CrossRefPubMedGoogle Scholar
  248. 248.
    Saitoh F, Tian QB, Okano A, Sakagami H, Kondo H, Suzuki T. NIDD, a novel DHHC-containing protein, targets neuronal nitric-oxide synthase (nNOS) to the synaptic membrane through a PDZ-dependent interaction and regulates nNOS activity. J Biol Chem. 2004;279:29461–8.CrossRefPubMedGoogle Scholar
  249. 249.
    Salaris SC, Babbs CF, Voorhees 3rd WD. Methylene blue as an inhibitor of superoxide generation by xanthine oxidase. A potential new drug for the attenuation of ischemia/reperfusion injury. Biochem Pharmacol. 1991;42:499–506.CrossRefPubMedGoogle Scholar
  250. 250.
    Salter M, Duffy C, Garthwaite J, Strijbos PJ. Substantial regional and hemispheric differences in brain nitric oxide synthase (NOS) inhibition following intracerebroventricular administration of N omega-nitro-L-arginine (L-NA) and its methyl ester (L-NAME). Neuropharmacology. 1995;34:639–49.CrossRefPubMedGoogle Scholar
  251. 251.
    Sanchez F, Moreno MN, Vacas P, Carretero J, Vazquez R. Swim stress enhances the NADPH-diaphorase histochemical staining in the paraventricular nucleus of the hypothalamus. Brain Res. 1999;828:159–62.CrossRefPubMedGoogle Scholar
  252. 252.
    Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, Weisstaub N, Lee J, Duman R, Arancio O, Belzung C, Hen R. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science. 2003;301:805–9.CrossRefPubMedGoogle Scholar
  253. 253.
    Sattler R, Xiong Z, Lu WY, Hafner M, MacDonald JF, Tymianski M. Specific coupling of NMDA receptor activation to nitric oxide neurotoxicity by PSD-95 protein. Science. 1999;284:1845–8.CrossRefPubMedGoogle Scholar
  254. 254.
    Schmidt HH, Lohmann SM, Walter U. The nitric oxide and cGMP signal transduction system: regulation and mechanism of action. Biochim Biophys Acta. 1993;1178:153–75.CrossRefPubMedGoogle Scholar
  255. 255.
    Schmidt HH, Pollock JS, Nakane M, Forstermann U, Murad F. Ca2+/calmodulin-regulated nitric oxide synthases. Cell Calcium. 1992;13:427–34.CrossRefPubMedGoogle Scholar
  256. 256.
    Schuman EM, Madison DV. A requirement for the intercellular messenger nitric oxide in long-term potentiation. Science. 1991;254:1503–6.CrossRefPubMedGoogle Scholar
  257. 257.
    Segovia G, Del Arco A, Mora F. Endogenous glutamate increases extracellular concentrations of dopamine, GABA, and taurine through NMDA and AMPA/kainate receptors in striatum of the freely moving rat: a microdialysis study. J Neurochem. 1997;69:1476–83.CrossRefPubMedGoogle Scholar
  258. 258.
    Segovia G, Del Arco A, Mora F. Role of glutamate receptors and glutamate transporters in the regulation of the glutamate-glutamine cycle in the awake rat. Neurochem Res. 1999;24:779–83.CrossRefPubMedGoogle Scholar
  259. 259.
    Segovia G, Porras A, Mora F. Effects of a nitric oxide donor on glutamate and GABA release in striatum and hippocampus of the conscious rat. Neuroreport. 1994;5:1937–40.CrossRefPubMedGoogle Scholar
  260. 260.
    Selley ML. Increased (E)-4-hydroxy-2-nonenal and asymmetric dimethylarginine concentrations and decreased nitric oxide concentrations in the plasma of patients with major depression. J Affect Disord. 2004;80:249–56.CrossRefPubMedGoogle Scholar
  261. 261.
    Shariful Islam ATM, Kuraoka A, Kawabuchi M. Morphological basis of nitric oxide production and its correlation with the polysialylated precursor cells in the dentate gyrus of the adult guinea pig hippocampus. Anat Sci Int. 2003;78:98–103.CrossRefGoogle Scholar
  262. 262.
    Shimabukuro M, Ohneda M, Lee Y, Unger RH. Role of nitric oxide in obesity-induced beta cell disease. J Clin Invest. 1997;100:290–5.CrossRefPubMedPubMedCentralGoogle Scholar
  263. 263.
    Siepmann M, Grossmann J, Muck-Weymann M, Kirch W. Effects of sertraline on autonomic and cognitive functions in healthy volunteers. Psychopharmacology (Berl). 2003;168:293–8.CrossRefGoogle Scholar
  264. 264.
    Silva M, Aguiar DC, Diniz CR, Guimaraes FS, Joca SR. Neuronal NOS inhibitor and conventional antidepressant drugs attenuate stress-induced fos expression in overlapping brain regions. Cell Mol Neurobiol. 2012;32:443–53.CrossRefPubMedGoogle Scholar
  265. 265.
    Simonian SX, Herbison AE. Localization of neuronal nitric oxide synthase-immunoreactivity within sub-populations of noradrenergic A1 and A2 neurons in the rat. Brain Res. 1996;732:247–52.CrossRefPubMedGoogle Scholar
  266. 266.
    Singewald N, Sinner C, Hetzenauer A, Sartori SB, Murck H. Magnesium-deficient diet alters depression- and anxiety-related behavior in mice – influence of desipramine and Hypericum perforatum extract. Neuropharmacology. 2004;47:1189–97.CrossRefPubMedGoogle Scholar
  267. 267.
    Spiacci Jr A, Kanamaru F, Guimaraes FS, Oliveira RM. Nitric oxide-mediated anxiolytic-like and antidepressant-like effects in animal models of anxiety and depression. Pharmacol Biochem Behav. 2008;88:247–55.CrossRefPubMedGoogle Scholar
  268. 268.
    Spolidorio PC, Echeverry MB, Iyomasa M, Guimaraes FS, Del Bel EA. Anxiolytic effects induced by inhibition of the nitric oxide-cGMP pathway in the rat dorsal hippocampus. Psychopharmacology (Berl). 2007;195:183–92.CrossRefGoogle Scholar
  269. 269.
    Srivastava N, Barthwal MK, Dalal PK, Agarwal AK, Nag D, Seth PK, Srimal RC, Dikshit M. A study on nitric oxide, beta-adrenergic receptors and antioxidant status in the polymorphonuclear leukocytes from the patients of depression. J Affect Disord. 2002;72:45–52.CrossRefPubMedGoogle Scholar
  270. 270.
    Stamler JS. Redox signaling: nitrosylation and related target interactions of nitric oxide. Cell. 1994;78:931–6.CrossRefPubMedGoogle Scholar
  271. 271.
    Stamler JS. S-nitrosothiols and the bioregulatory actions of nitrogen oxides through reactions with thiol groups. Curr Top Microbiol Immunol. 1995;196:19–36.PubMedGoogle Scholar
  272. 272.
    Stamler JS, Lamas S, Fang FC. Nitrosylation the prototypic redox-based signaling mechanism. Cell. 2001;106:675–83.CrossRefPubMedGoogle Scholar
  273. 273.
    Stanford SC, Stanford BJ, Gillman PK. Risk of severe serotonin toxicity following co-administration of methylene blue and serotonin reuptake inhibitors: an update on a case report of post-operative delirium. J Psychopharmacol (Oxf). 2009;24:1433–8.Google Scholar
  274. 274.
    Strasser A, McCarron RM, Ishii H, Stanimirovic D, Spatz M. L-arginine induces dopamine release from the striatum in vivo. Neuroreport. 1994;5:2298–300.CrossRefPubMedGoogle Scholar
  275. 275.
    Suarez-Pinzon WL, Mabley JG, Strynadka K, Power RF, Szabo C, Rabinovitch A. An inhibitor of inducible nitric oxide synthase and scavenger of peroxynitrite prevents diabetes development in NOD mice. J Autoimmun. 2001;16:449–55.CrossRefPubMedGoogle Scholar
  276. 276.
    Sullivan PF, de Geus EJ, Willemsen G, James MR, Smit JH, Zandbelt T, Arolt V, Baune BT, Blackwood D, Cichon S, Coventry WL, Domschke K, Farmer A, Fava M, Gordon SD, He Q, Heath AC, Heutink P, Holsboer F, Hoogendijk WJ, Hottenga JJ, Hu Y, Kohli M, Lin D, Lucae S, Macintyre DJ, Maier W, McGhee KA, McGuffin P, Montgomery GW, Muir WJ, Nolen WA, Nothen MM, Perlis RH, Pirlo K, Posthuma D, Rietschel M, Rizzu P, Schosser A, Smit AB, Smoller JW, Tzeng JY, van Dyck R, Verhage M, Zitman FG, Martin NG, Wray NR, Boomsma DI, Penninx BW. Genome-wide association for major depressive disorder: a possible role for the presynaptic protein piccolo. Mol Psychiatry. 2009;14:359–75.CrossRefPubMedGoogle Scholar
  277. 277.
    Suzuki E, Yagi G, Nakaki T, Kanba S, Asai M. Elevated plasma nitrate levels in depressive states. J Affect Disord. 2001;63:221–4.CrossRefPubMedGoogle Scholar
  278. 278.
    Suzuki E, Yoshida Y, Shibuya A, Miyaoka H. Nitric oxide involvement in depression during interferon-alpha therapy. Int J Neuropsychopharmacol. 2003;6:415–9.CrossRefPubMedGoogle Scholar
  279. 279.
    Szewczyk B, Poleszak E, Sowa-Kućna M, Siwek M, Dudek D, Ryszewska-Pokraśniewicz B, Radziwoń-Zaleska M, Opoka W, Czekaj J, Pilc A, Nowak G. Antidepressant activity of zinc and magnesium in view of the current hypotheses of antidepressant action. Pharmacol Rep. 2008;60:588–99.PubMedGoogle Scholar
  280. 280.
    Takano H, Manchikalapudi S, Tang XL, Qiu Y, Rizvi A, Jadoon AK, Zhang Q, Bolli R. Nitric oxide synthase is the mediator of late preconditioning against myocardial infarction in conscious rabbits. Circulation. 1998;98:441–9.CrossRefPubMedGoogle Scholar
  281. 281.
    Taksande BG, Kotagale NR, Tripathi SJ, Ugale RR, Chopde CT. Antidepressant like effect of selective serotonin reuptake inhibitors involve modulation of imidazoline receptors by agmatine. Neuropharmacology. 2009;57:415–24.CrossRefPubMedGoogle Scholar
  282. 282.
    Tanda K, Nishi A, Matsuo N, Nakanishi K, Yamasaki N, Sugimoto T, Toyama K, Takao K, Miyakawa T. Abnormal social behavior, hyperactivity, impaired remote spatial memory, and increased D1-mediated dopaminergic signaling in neuronal nitric oxide synthase knockout mice. Mol Brain. 2009;2:19.CrossRefPubMedPubMedCentralGoogle Scholar
  283. 283.
    Thomsen LL. Investigations into the role of nitric oxide and the large intracranial arteries in migraine headache. Cephalgia. 1997;17:873–95.CrossRefGoogle Scholar
  284. 284.
    Thomsen LL, Olesen J. Nitric oxide theory of migraine. Clin Neurosci. 1998;5:28–33.CrossRefPubMedGoogle Scholar
  285. 285.
    Tokarski K, Bobula B, Wabno J, Hess G. Repeated administration of imipramine attenuates glutamatergic transmission in rat frontal cortex. Neuroscience. 2008;153:789–95.CrossRefPubMedGoogle Scholar
  286. 286.
    Tsuchiya T, Kishimoto J, Nakayama Y. Marked increases in neuronal nitric oxide synthase (nNOS) mRNA and NADPH-diaphorase histostaining in adrenal cortex after immobilization stress in rats. Psychoneuroendocrinology. 1996;21:287–93.CrossRefPubMedGoogle Scholar
  287. 287.
    Vallebuona F, Raiteri M. Extracellular cGMP in the hippocampus of freely moving rats as an index of nitric oxide (NO) synthase activity. J Neurosci. 1994;14:134–9.PubMedGoogle Scholar
  288. 288.
    Valtschanoff JG, Weinberg RJ, Kharazia VN, Schmidt HH, Nakane M, Rustioni A. Neurons in rat cerebral cortex that synthesize nitric oxide: NADPH diaphorase histochemistry, NOS immunocytochemistry, and colocalization with GABA. Neurosci Lett. 1993;157:157–61.CrossRefPubMedGoogle Scholar
  289. 289.
    Volke V, Wegener G, Bourin M, Vasar E. Antidepressant- and anxiolytic-like effects of selective neuronal NOS inhibitor 1-(2-trifluoromethylphenyl)-imidazole in mice. Behav Brain Res. 2003;140:141–7.CrossRefPubMedGoogle Scholar
  290. 290.
    Volke V, Wegener G, Vasar E. Augmentation of the NO-cGMP cascade induces anxiogenic-like effect in mice. J Physiol Pharmacol. 2003;54:653–60.PubMedGoogle Scholar
  291. 291.
    Volke V, Wegener G, Vasar E, Rosenberg R. Methylene blue inhibits hippocampal nitric oxide synthase activity in vivo. Brain Res. 1999;826:303–5.CrossRefPubMedGoogle Scholar
  292. 292.
    Wallerath T, Gath I, Aulitzky WE, Pollock JS, Kleinert H, Förstermann U. Identification of the NO synthase isoforms expressed in human neutrophil granulocytes, megakaryocytes and platelets. Thromb Haemost. 1997;77:163–7.PubMedGoogle Scholar
  293. 293.
    Wang D, An SC, Zhang X. Prevention of chronic stress-induced depression-like behavior by inducible nitric oxide inhibitor. Neurosci Lett. 2008;433:59–64.CrossRefPubMedGoogle Scholar
  294. 294.
    Wang D, Yang XP, Liu YH, Carretero OA, LaPointe MC. Reduction of myocardial infarct size by inhibition of inducible nitric oxide synthase. Am J Hypertens. 1999;12:174–82.CrossRefPubMedGoogle Scholar
  295. 295.
    Wegener G, Harvey BH, Bonefeld B, Muller HK, Volke V, Overstreet DH, Elfving B. Increased stress-evoked nitric oxide signalling in the Flinders sensitive line (FSL) rat: a genetic animal model of depression. Int J Neuropsychopharmacol. 2010;13:461–73.CrossRefPubMedGoogle Scholar
  296. 296.
    Wegener G, Rujescu D. The current development of CNS drug research. Int J Neuropsychopharmacol. 2013;16:1687–93.CrossRefPubMedGoogle Scholar
  297. 297.
    Wegener G, Volke V, Bandpey Z, Rosenberg R. Nitric oxide modulates lithium-induced conditioned taste aversion. Behav Brain Res. 2001;118:195–200.CrossRefPubMedGoogle Scholar
  298. 298.
    Wegener G, Volke V, Harvey BH, Rosenberg R. Local, but not systemic, administration of serotonergic antidepressants decreases hippocampal nitric oxide synthase activity. Brain Res. 2003;959:128–34.CrossRefPubMedGoogle Scholar
  299. 299.
    Wegener G, Volke V, Rosenberg R. Endogenous nitric oxide decreases hippocampal levels of serotonin and dopamine in vivo. Br J Pharmacol. 2000;130:575–80.CrossRefPubMedPubMedCentralGoogle Scholar
  300. 300.
    Weitzdoerfer R, Hoeger H, Engidawork E, Engelmann M, Singewald N, Lubec G, Lubec B. Neuronal nitric oxide synthase knock-out mice show impaired cognitive performance. Nitric Oxide. 2004;10:130–40.CrossRefPubMedGoogle Scholar
  301. 301.
    Wiesinger H. Arginine metabolism and the synthesis of nitric oxide in the nervous system. Prog Neurobiol. 2001;64:365–91.CrossRefPubMedGoogle Scholar
  302. 302.
    Wiklund NP, Cellek S, Leone AM, Iversen HH, Gustafsson LE, Brundin L, Furst VW, Flock A, Moncada S. Visualisation of nitric oxide released by nerve stimulation. J Neurosci Res. 1997;47:224–32.CrossRefPubMedGoogle Scholar
  303. 303.
    Wiley JL, Willmore CB. Effects of nitric oxide synthase inhibitors on timing and short-term memory in rats. Behav Pharmacol. 2000;11:421–9.CrossRefPubMedGoogle Scholar
  304. 304.
    Wittchen HU, Jacobi F, Rehm J, Gustavsson A, Svensson M, Jonsson B, Olesen J, Allgulander C, Alonso J, Faravelli C, Fratiglioni L, Jennum P, Lieb R, Maercker A, van Os J, Preisig M, Salvador-Carulla L, Simon R, Steinhausen HC. The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur Neuropsychopharmacol. 2011;21:655–79.CrossRefPubMedGoogle Scholar
  305. 305.
    Xing G, Chavko M, Zhang LX, Yang S, Post RM. Decreased calcium-dependent constitutive nitric oxide synthase (cNOS) activity in prefrontal cortex in schizophrenia and depression. Schizophr Res. 2002;58:21–30.CrossRefPubMedGoogle Scholar
  306. 306.
    Yang B, Larson DF, Watson RR. Modulation of iNOS activity in age-related cardiac dysfunction. Life Sci. 2004;75:655–67.CrossRefPubMedGoogle Scholar
  307. 307.
    Yang XC, Reis DJ. Agmatine selectively blocks the N-methyl-D-aspartate subclass of glutamate receptor channels in rat hippocampal neurons. J Pharmacol Exp Ther. 1999;288:544–9.PubMedGoogle Scholar
  308. 308.
    Yildiz Akar F, Celikyurt IK, Ulak G, Mutlu O. Effects of L-arginine on 7-nitroindazole-induced reference and working memory performance of rats. Pharmacology. 2009;84:211–8.CrossRefPubMedGoogle Scholar
  309. 309.
    Yildiz Akar F, Ulak G, Tanyeri P, Erden F, Utkan T, Gacar N. 7-Nitroindazole, a neuronal nitric oxide synthase inhibitor, impairs passive-avoidance and elevated plus-maze memory performance in rats. Pharmacol Biochem Behav. 2007;87:434–43.CrossRefPubMedGoogle Scholar
  310. 310.
    Yildiz F, Erden BF, Ulak G, Utkan T, Gacar N. Antidepressant-like effect of 7-nitroindazole in the forced swimming test in rats. Psychopharmacology (Berl). 2000;149:41–4.CrossRefGoogle Scholar
  311. 311.
    Yu YW, Chen TJ, Wang YC, Liou YJ, Hong CJ, Tsai SJ. Association analysis for neuronal nitric oxide synthase gene polymorphism with major depression and fluoxetine response. Neuropsychobiology. 2003;47:137–40.CrossRefPubMedGoogle Scholar
  312. 312.
    Yun HY, Gonzalez-Zulueta M, Dawson VL, Dawson TM. Nitric oxide mediates N-methyl-D-aspartate receptor-induced activation of p21ras. Proc Natl Acad Sci U S A. 1998;95:5773–8.CrossRefPubMedPubMedCentralGoogle Scholar
  313. 313.
    Zaragoza C, Ocampo C, Saura M, Leppo M, Wei XQ, Quick R, Moncada S, Liew FY, Lowenstein CJ. The role of inducible nitric oxide synthase in the host response to Coxsackievirus myocarditis. Proc Natl Acad Sci U S A. 1998;95:2469–74.CrossRefPubMedPubMedCentralGoogle Scholar
  314. 314.
    Zaragoza C, Ocampo CJ, Saura M, Bao C, Leppo M, Lafond-Walker A, Thiemann DR, Hruban R, Lowenstein CJ. Inducible nitric oxide synthase protection against coxsackievirus pancreatitis. J Immunol. 1999;163:5497–504.PubMedGoogle Scholar
  315. 315.
    Zarate Jr CA, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006;63:856–64.CrossRefPubMedGoogle Scholar
  316. 316.
    Zhang J, Huang XY, Ye ML, Luo CX, Wu HY, Hu Y, Zhou QG, Wu DL, Zhu LJ, Zhu DY. Neuronal nitric oxide synthase alteration accounts for the role of 5-HT1A receptor in modulating anxiety-related behaviors. J Neurosci. 2010;30:2433–41.CrossRefPubMedGoogle Scholar
  317. 317.
    Zhang R, Zhang L, Zhang Z, Wang Y, Lu M, LaPointe M, Chopp M. A nitric oxide donor induces neurogenesis and reduces functional deficits after stroke in rats. Ann Neurol. 2001;50:602–11.CrossRefPubMedGoogle Scholar
  318. 318.
    Zhou QG, Hu Y, Hua Y, Hu M, Luo CX, Han X, Zhu XJ, Wang B, Xu JS, Zhu DY. Neuronal nitric oxide synthase contributes to chronic stress-induced depression by suppressing hippocampal neurogenesis. J Neurochem. 2007;103:1843–54.CrossRefPubMedGoogle Scholar
  319. 319.
    Zhu XJ, Hua Y, Jiang J, Zhou QG, Luo CX, Han X, Lu YM, Zhu DY. Neuronal nitric oxide synthase-derived nitric oxide inhibits neurogenesis in the adult dentate gyrus by down-regulating cyclic AMP response element binding protein phosphorylation. Neuroscience. 2006;141:827–36.CrossRefPubMedGoogle Scholar
  320. 320.
    Zomkowski AD, Hammes L, Lin J, Calixto JB, Santos AR, Rodrigues AL. Agmatine produces antidepressant-like effects in two models of depression in mice. Neuroreport. 2002;13:387–91.CrossRefPubMedGoogle Scholar
  321. 321.
    Zou LB, Yamada K, Tanaka T, Kameyama T, Nabeshima T. Nitric oxide synthase inhibitors impair reference memory formation in a radial arm maze task in rats. Neuropharmacology. 1998;37:323–30.CrossRefPubMedGoogle Scholar

Copyright information

© Springer India 2016

Authors and Affiliations

  1. 1.Translational Neuropsychiatry Unit, Department of Clinical MedicineAarhus UniversityAarhusDenmark
  2. 2.Centre for Pharmaceutical Excellence, School of PharmacyNorth West UniversityPotchefstroomSouth Africa
  3. 3.Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão PretoUniversity of São PauloSão PauloBrazil

Personalised recommendations