Pharmacological manipulation of kynurenic acid: Potential in the treatment of psychiatric disorders

CNS Drugs

Volumn 23, Issue 2, 2009, Pages 91-101

  Erhardt, Sophie ^a   Olsson, Sara K ^a   Engberg, Göran ^a  

^a KAROLINSKA INSTITUTE   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

3 HYDROXYKYNURENINE; AMINOOXYACETIC ACID; AMPA RECEPTOR; BUNGAROTOXIN RECEPTOR; CYCLOOXYGENASE 1; CYCLOOXYGENASE 2; DICLOFENAC; DIZOCILPINE; DOPAMINE; ENZYME INHIBITOR; GLUTAMATE RECEPTOR; HOMOVANILLIC ACID; INDOMETACIN; KAINIC ACID RECEPTOR; KYNURENIC ACID; KYNURENINE; KYNURENINE 3 MONOOXYGENASE; KYNURENINE AMINOTRANSFERASE; MELOXICAM; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; NICOTINIC RECEPTOR; PARECOXIB; PHENCYCLIDINE; PNU 156561A; PROBENECID; QUINOLINIC ACID; RO 618048; SDZ 220581; TRYPTOPHAN; UNCLASSIFIED DRUG; UNINDEXED DRUG;

COGNITION; DOPAMINERGIC NERVE CELL; HUMAN; MENTAL DISEASE; MENTAL PATIENT; NEUROPSYCHIATRY; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REVIEW; SCHIZOPHRENIA;

ANIMALS; COGNITION DISORDERS; EXCITATORY AMINO ACID ANTAGONISTS; HUMANS; KYNURENIC ACID; KYNURENINE; MENTAL DISORDERS; SCHIZOPHRENIA;

EID: 59149090373     PISSN: 11727047     EISSN: None     Source Type: Journal    
DOI: 10.2165/00023210-200923020-00001     Document Type: Review

References (134)

1. Erhardt S, Schwieler L, Engberg G. Kynurenic acid and schizophrenia. Adv Exp Med Biol 2003; 527: 155-65
2. Erhardt S, Schwieler L, Nilsson L, et al. The kynurenic acid hypothesis of schizophrenia. Physiol Behav 2007 Sep 10; 92 (1-2): 203-9
3. Stone TW. Neuropharmacology of quinolinic and kynurenic acids. Pharmacol Rev 1993 Sep; 45 (3): 309-79
4. Perkins MN, Stone TW. An iontophoretic investigation of the actions of convulsant kynurenines and their interaction with the endogenous excitant quinolinic acid. Brain Res 1982 Sep 9; 247 (1): 184-7
5. Liebig J. Uber kynurensäure. Justus Liebigs Ann Chem 1853; 86: 125-6
6. Ellinger A. Die entstehung der Kynurensaure. Z Physiol Chem 1904; 43: 325-37
7. Beadle GW, Mitchell HK, Nyc JF. Kynurenine as an intermediate in the formation of nicotinic acid from tryptophane by neurospora. Proc Natl Acad Sci U S A 1947 Jun; 33 (6): 155-8
8. Wolf H. Studies on tryptophan metabolism in man: the effect of hormones and vitamin B6 on urinary excretion of metabolites of the kynurenine pathway. Scand J Clin Lab Invest 1974; 136: 1-186
9. Mehler AH, Knox WE. The conversion of tryptophan to kynurenine in liver: II. The enzymatic hydrolysis of formylkynurenine. J Biol Chem 1950 Nov; 187 (1): 431-8
10. Moroni F. Tryptophan metabolism and brain function: focus on kynurenine and other indole metabolites. Eur J Pharmacol 1999 Jun 30; 375 (1-3): 87-100
11. Moroni F, Russi P, Lombardi G, et al. Presence of kynurenic acid in the mammalian brain. J Neurochem 1988 Jul; 51 (1): 177-80
12. Turski WA, Nakamura M, Todd WP, et al. Identification and quantification of kynurenic acid in human brain tissue. Brain Res 1988 Jun 28; 454 (1-2): 164-9
13. Okuno E, Nakamura M, Schwarcz R. Two kynurenine aminotransferases in human brain. Brain Res 1991 Mar 1; 542 (2): 307-12
14. Schmidt W, Guidetti P, Okuno E, et al. Characterization of human brain kynurenine aminotransferases using [3H]-kynurenine as a substrate. Neuroscience 1993 Jul; 55 (1): 177-84
15. Guidetti P, Okuno E, Schwarcz R. Characterization of rat brain kynurenine aminotransferases I and II. J Neurosci Res 1997 Nov 1; 50 (3): 457-65
16. Yu P, Li Z, Zhang L, et al. Characterization of kynurenine aminotransferase III, a novel member of a phylogenetically conserved KAT family. Gene 2006 Jan 3; 365: 111-8
17. Ceresoli-Borroni G, Guidetti P, Schwarcz R. Acute and chronic changes in kynurenate formation following an intrastriatal quinolinate injection in rats. J Neural Transm 1999; 106 (3-4): 229-42
18. Okuno E, Schmidt W, Parks DA, et al. Measurement of rat brain kynurenine aminotransferase at physiological kynurenine concentrations. J Neurochem 1991 Aug; 57 (2): 533-40
19. Du F, Schmidt W, Okuno E, et al. Localization of kynurenine aminotransferase immunoreactivity in the rat hippocampus. J Comp Neurol 1992 Jul 15; 321 (3): 477-87
20. Guidetti P, Amori L, Sapko MT, et al. Mitochondrial aspartate aminotransferase: a third kynurenate-producing enzyme in the mammalian brain. J Neurochem 2007 Jul; 102 (1): 103-11
21. Fukui S, Schwarcz R, Rapoport SI, et al. Blood-brain barrier transport of kynurenines: implications for brain synthesis and metabolism. J Neurochem 1991 Jun; 56 (6): 2007-17
22. Christensen HN. Organic ion transport during seven decades: the amino acids. Biochim Biophys Acta 1984 Sep 3; 779 (3): 255-69
23. Speciale C, Hares K, Schwarcz R, et al. High-affinity uptake of L-kynurenine by a Na+-independent transporter of neutral amino acids in astrocytes. J Neurosci 1989 Jun; 9 (6): 2066-72
24. Swartz KJ, During MJ, Freese A, et al. Cerebral synthesis and release of kynurenic acid: an endogenous antagonist of excitatory amino acid receptors. J Neurosci 1990 Sep; 10 (9): 2965-73
25. Gramsbergen JB, Hodgkins PS, Rassoulpour A, et al. Brainspecific modulation of kynurenic acid synthesis in the rat. J Neurochem 1997 Jul; 69 (1): 290-8
26. Moroni F, Russi P, Carla V, et al. Kynurenic acid is present in the rat brain and its content increases during development and aging processes. Neurosci Lett 1988 Nov 22; 94 (1-2): 145-50
27. Gramsbergen JB, Schmidt W, Turski WA, et al. Age-related changes in kynurenic acid production in rat brain. Brain Res 1992 Aug 14; 588 (1): 1-5
28. Takahashi H, Kaihara M, Price JM. The conversion of kynurenic acid to quinaldic acid by humans and rats. J Biol Chem 1956; 223: 705-8
29. Turski WA, Schwarcz R. On the disposition of intra-hippocampally injected kynurenic acid in the rat. Exp Brain Res 1988; 71 (3): 563-7
30. Chang YF, Cauley RK, Chang JD, et al. L-alpha-aminoadipate inhibits kynurenate synthesis in rat brain hippocampus and tissue culture. Neurochem Res 1997 Jul; 22 (7): 825-9
31. Russi P, Alesiani M, Lombardi G, et al. Nicotinylalanine increases the formation of kynurenic acid in the brain and antagonizes convulsions. J Neurochem 1992 Dec; 59 (6): 2076-80
32. Speciale C, Wu HQ, Cini M, et al. (R,S)-3,4-dichloro-benzoylalanine (FCE 28833A) causes a large and persistent increase in brain kynurenic acid levels in rats. Eur J Pharmacol 1996 Nov 21; 315 (3): 263-7
33. Schwieler L, Erhardt S, Erhardt C, et al. Prostaglandin-mediated control of rat brain kynurenic acid synthesis: opposite actions by COX-1 and COX-2 isoforms. J Neural Transm 2005 Jul; 112 (7): 863-72
34. Schwieler L, Erhardt S, Nilsson L, et al. Effects of COX-1 and COX-2 inhibitors on the firing of rat midbrain dopaminergic neurons: possible involvement of endogenous kynurenic acid. Synapse 2006 Apr; 59 (5): 290-8
35. Edwards SR, Mather LE, Lin Y, et al. Glutamate and kynurenate in the rat central nervous system following treatments with tail ischaemia or diclofenac. J Pharm Pharmacol 2000 Jan; 52 (1): 59-66
36. Speciale C, Wu HQ, Gramsbergen JB, et al. Determination of extracellular kynurenic acid in the striatum of unanesthetized rats: effect of aminooxyacetic acid. Neurosci Lett 1990 Aug 14; 116 (1-2): 198-203
37. Parsons CG, Danysz W, Quack G, et al. Novel systemically active antagonists of the glycine site of the N-methyl-D-aspartate receptor: electrophysiological, biochemical and behavioral characterization. J Pharmacol Exp Ther 1997 Dec; 283 (3): 1264-75
38. Kessler M, Terramani T, Lynch G, et al. A glycine site associated with N-methyl-D-aspartic acid receptors: characterization and identification of a new class of antagonists. J Neurochem 1989 Apr; 52 (4): 1319-28
39. Prescott C, Weeks AM, Staley KJ, et al. Kynurenic acid has a dual action on AMPA receptor responses. Neurosci Lett 2006 Jul 10; 402 (1-2): 108-12
40. Hilmas C, Pereira EF, Alkondon M, et al. The brain metabolite kynurenic acid inhibits alpha7 nicotinic receptor activity and increases non-alpha7 nicotinic receptor expression: physiopathological implications. J Neurosci 2001 Oct 1; 21 (19): 7463-73
41. Alkondon M, Pereira EF, Yu P, et al. Targeted deletion of the kynurenine aminotransferase II gene reveals a critical role of endogenous kynurenic acid in the regulation of synaptic transmission via alpha7 nicotinic receptors in the hippocampus. J Neurosci 2004 May 12; 24 (19): 4635-48
42. Alkondon M, Pereira EF, Potter MC, et al. Strain-specific nicotinic modulation of glutamatergic transmission in the CA1 field of the rat hippocampus: August Copenhagen Irish versus Sprague-Dawley. J Neurophysiol 2007 Feb; 97 (2): 1163-70
43. Stone TW. Kynurenic acid blocks nicotinic synaptic transmission to hippocampal interneurons in young rats. Eur J Neurosci 2007 May; 25 (9): 2656-65
44. Foster AC, Vezzani A, French ED, et al. Kynurenic acid blocks neurotoxicity and seizures induced in rats by the related brain metabolite quinolinic acid. Neurosci Lett 1984 Aug 10; 48 (3): 273-8
45. Hajos M, Engberg G. Kynurenic acid blocks chemogenic nociception. J Pharm Pharmacol 1990 May; 42 (5): 373-4
46. Hajos M, Engberg G. A role of excitatory amino acids in the activation of locus coeruleus neurons following cutaneous thermal stimuli. Brain Res 1990 Jun 25; 521 (1-2): 325-8
47. Nozaki K, Beal MF. Neuroprotective effects of L-kynurenine on hypoxia-ischemia and NMDA lesions in neonatal rats. J Cereb Blood Flow Metab 1992 May; 12 (3): 400-7
48. Carpenedo R, Chiarugi A, Russi P, et al. Inhibitors of kynurenine hydroxylase and kynureninase increase cerebral formation of kynurenate and have sedative and anti-convulsant activities. Neuroscience 1994 Jul; 61 (2): 237-43
49. Wu HQ, Guidetti P, Goodman JH, et al. Kynurenergic manipulations influence excitatory synaptic function and excitotoxic vulnerability in the rat hippocampus in vivo. Neuroscience 2000; 97 (2): 243-51
50. Connick JH, Heywood GC, Sills GJ, et al. Nicotinylalanine increases cerebral kynurenic acid content and has anti-convulsant activity. Gen Pharmacol 1992 Mar; 23 (2): 235-9
51. Erhardt S, Hajos M, Lindberg A, et al. Nicotine-induced excitation of locus coeruleus neurons is blocked by elevated levels of endogenous kynurenic acid. Synapse 2000 Aug; 37 (2): 104-8
52. Erhardt S, Oberg H, Engberg G. Pharmacologically elevated levels of endogenous kynurenic acid prevent nicotine-induced activation of nigral dopamine neurons. Naunyn Schmiedebergs Arch Pharmacol 2001 Jan; 363 (1): 21-7
53. Erhardt S, Oberg H, Mathe JM, et al. Pharmacological elevation of endogenous kynurenic acid levels activates nigral dopamine neurons. Amino Acids 2001; 20 (4): 353-62
54. Erhardt S, Schwieler L, Emanuelsson C, et al. Endogenous kynurenic acid disrupts prepulse inhibition. Biol Psychiatry 2004 Aug 15; 56 (4): 255-60
55. Erhardt S, Engberg G. Excitation of nigral dopamine neurons by the GABA(A) receptor agonist muscimol is mediated via release of glutamate. Life Sci 2000 Sep 1; 67 (15): 1901-11
56. Erhardt S, Engberg G. Increased phasic activity of dopaminergic neurones in the rat ventral tegmental area following pharmacologically elevated levels of endogenous kynurenic acid. Acta Physiol Scand 2002 May; 175 (1): 45-53
57. Nilsson LK, Schwieler L, Engberg G, et al. Activation of noradrenergic locus coeruleus neurons by clozapine and haloperidol: involvement of glutamatergic mechanisms. Int J Neuropsychopharmacol 2005; 8 (3): 329-39
58. Nilsson LK, Linderholm KR, Erhardt S. Subchronic treatment with kynurenine and probenecid: effects on prepulse inhibition and firing of midbrain dopamine neurons. J Neural Transm 2006 May; 113 (5): 557-71
59. Erhardt S, Schwieler L, Engberg G. Excitatory and inhibitory responses of dopamine neurons in the ventral tegmental area to nicotine. Synapse 2002 Mar 15; 43 (4): 227-37
60. Schwarcz R, Du F, Schmidt W, et al. Kynurenic acid: a potential pathogen in brain disorders. Ann N Y Acad Sci 1992 May 11; 648: 140-53
61. Stone TW. Kynurenines in the CNS: from endogenous obscurity to therapeutic importance. Prog Neurobiol 2001 Jun; 64 (2): 185-218
62. Schwieler L, Linderholm KR, Nilsson-Todd LK, et al. Clozapine interacts with the glycine site of the NMDA receptor: electrophysiological studies of dopamine neurons in the rat ventral tegmental area. Life Sci 2008; 83 (5-6): 170-5
63. Curatolo L, Caccia C, Speciale C, et al. Modulation of extracellular kynurenic acid content by excitatory amino acids in primary cultures of rat astrocytes. Adv Exp Med Biol 1996; 398: 273-6
64. Guillemin GJ, Kerr SJ, Smythe GA, et al. Kynurenine pathway metabolism in human astrocytes: a paradox for neuronal protection. J Neurochem 2001 Aug; 78 (4): 842-53
65. Kiss C, Ceresoli-Borroni G, Guidetti P, et al. Kynurenate production by cultured human astrocytes. J Neural Transm 2003 Jan; 110 (1): 1-14
66. Coyle JT, Schwarcz R. Mind glue: implications of glial cell biology for psychiatry. Arch Gen Psychiatry 2000 Jan; 57 (1): 90-3
67. Newman EA. New roles for astrocytes: regulation of synaptic transmission. Trends Neurosci 2003 Oct; 26 (10): 536-42
68. Rassoulpour A, Wu HQ, Ferre S, et al. Nanomolar concentrations of kynurenic acid reduce extracellular dopamine levels in the striatum. J Neurochem 2005 May; 93 (3): 762-5
69. Linderholm KR, Andersson A, Olsson S, et al. Activation of rat ventral tegmental area dopamine neurons by endogenous kynurenic acid: a pharmacological analysis. Neuropharmacology 2007 Dec; 53 (8): 918-24
70. French ED, Mura A, Wang T. MK-801, phencyclidine (PCP), and PCP-like drugs increase burst firing in rat A10 dopamine neurons: comparison to competitive NMDA antagonists. Synapse 1993 Feb; 13 (2): 108-16
71. French ED. Phencyclidine and the midbrain dopamine system: electrophysiology and behavior. Neurotoxicol Teratol 1994 Jul-Aug; 16 (4): 355-62
72. Baran H, Jellinger K, Deecke L. Kynurenine metabolism in Alzheimer's disease. J Neural Transm 1999; 106 (2): 165-81
73. Ogawa T, Matson WR, Bea lMF, et al. Kynurenine pathway abnormalities in Parkinson's disease. Neurology 1992 Sep; 42 (9): 1702-6
74. Beal MF, Matson WR, Storey E, et al. Kynurenic acid concentrations are reduced in Huntington's disease cerebral cortex. J Neurol Sci 1992 Mar; 108 (1): 80-7
75. Yamamoto H, Murakami H, Horiguchi K, et al. Studies on cerebrospinal fluid kynurenic acid concentrations in epileptic children. Brain Dev 1995 Sep-Oct; 17 (5): 327-9
76. Ilzecka J, Kocki T, Stelmasiak Z, et al. Endogenous protectant kynurenic acid in amyotrophic lateral sclerosis. Acta Neurol Scand 2003 Jun; 107 (6): 412-8
77. Demitrack MA, Heyes MP, Altemus M, et al. Cerebrospinal fluid levels of kynurenine pathway metabolites in patients with eating disorders: relation to clinical and biochemical variable. Biol Psychiatry 1995 Apr 15; 37 (8): 512-20
78. Erhardt S, Blennow K, Nordin C, et al. Kynurenic acid levels are elevated in the cerebrospinal fluid of patients with schizophrenia. Neurosci Lett 2001 Nov 2; 313 (1-2): 96-8
79. Nilsson LK, Linderholm KR, Engberg G, et al. Elevated levels of kynurenic acid in the cerebrospinal fluid of male patients with schizophrenia. Schizophr Res 2005 Dec 15; 80 (2-3): 315-22
80. Schwarcz R, Rassoulpour A, Wu HQ, et al. Increased cortical kynurenate content in schizophrenia. Biol Psychiatry 2001 Oct 1; 50 (7): 521-30
81. Muller N, Schwarz M. Schizophrenia as an inflammation-mediated dysbalance of glutamatergic neurotransmission. Neurotox Res 2006 Oct; 10 (2): 131-48
82. Swartz KJ, Matson WR, MacGarvey U, et al. Measurement of kynurenic acid in mammalian brain extracts and cerebrospinal fluid by high-performance liquid chromatography with fluorometric and coulometric electrode array detection. Anal Biochem 1990 Mar; 185 (2): 363-76
83. Carlsson A, Waters N, Holm-Waters S, et al. Interactions between monoamines, glutamate, and GABA in schizophrenia: new evidence. Annu Rev Pharmacol Toxicol 2001; 41: 237-60
84. Javitt DC, Zukin SR. Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry 1991 Oct; 148 (10): 1301-8
85. Albers GW, Clark WM, Atkinson RP, et al. Dose escalation study of the NMDA glycine-site antagonist licostinel in acute ischemic stroke. Stroke 1999 Mar; 30 (3): 508-13
86. Geyer MA, Krebs-Thomson K, Braff DL, et al. Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review. Psychopharmacology (Berl) 2001 Jul; 156 (2-3): 117-54
87. Grace AA. Regulation of spontaneous activity and oscillatory spike firing in rat midbrain dopamine neurons recorded in vitro. Synapse 1991 Mar; 7 (3): 221-34
88. Davis KL, Kahn RS, Ko G, et al. Dopamine in schizophrenia: a review and reconceptualization. Am J Psychiatry 1991 Nov; 148 (11): 1474-86
89. Jentsch JD, Roth RH. The neuropsychopharmacology of phencyclidine: from NMDA receptor hypofunction to the dopamine hypothesis of schizophrenia. Neuropsychopharmacology 1999 Mar; 20 (3): 201-25
90. Abi-Dargham A, Laruelle M. Mechanisms of action of second generation antipsychotic drugs in schizophrenia: insights from brain imaging studies. Eur Psychiatry 2005 Jan; 20 (1): 15-27
91. Olsson SK, Andersson AS, Linderholm KR, et al. Elevated levels of kynurenic acid change the dopaminergic response to amphetamine: implications for schizophrenia. Int J Neuropsychopharmacol. Epub 2008 Sep 17
92. Laruelle M, Abi-Dargham A. Dopamine as the wind of the psychotic fire: new evidence from brain imaging studies. J Psychopharmacol 1999 Dec; 13 (4): 358-71
93. Nilsson LK, Nordin C, Jönsson EG, et al. Cerebrospinal fluid kynurenic acid in male patients with schizophrenia: correlation with monoamine metabolites. Acta Neuropsychiatrica 2007; 19 (1): 45-52
94. Nilsson LK, Nordin C, Jonsson EG, et al. Cerebrospinal fluid kynurenic acid in male and female controls: correlation with monoamine metabolites and influences of confounding factors. J Psychiatr Res 2007 Jan-Feb; 41 (1-2): 144-51
95. Miller CL, Llenos IC, Dulay JR, et al. Expression of the kynurenine pathway enzyme tryptophan 2,3-dioxygenase is increased in the frontal cortex of individuals with schizophrenia. Neurobiol Dis 2004 Apr; 15 (3): 618-29
96. Roberts GW, Colter N, Lofthouse R, et al. Gliosis in schizophrenia: a survey. Biol Psychiatry 1986 Sep; 21 (11): 1043-50
97. Roberts GW, Colter N, Lofthouse R, et al. Is there gliosis in schizophrenia? Investigation of the temporal lobe. Biol Psychiatry 1987 Dec; 22 (12): 1459-68
98. Arnold SE, Franz BR, Trojanowski JQ, et al. Glial fibrillary acidic protein-immunoreactive astrocytosis in elderly patients with schizophrenia and dementia. Acta Neuropathol 1996; 91 (3): 269-77
99. Arnold SE, Trojanowski JQ, Gur RE, et al. Absence of neurodegeneration and neural injury in the cerebral cortex in a sample of elderly patients with schizophrenia. Arch Gen Psychiatry 1998 Mar; 55 (3): 225-32
100. Falkai P, Honer WG, David S, et al. No evidence for astrogliosis in brains of schizophrenic patients: a post-mortem study. Neuropathol Appl Neurobiol 1999 Feb; 25 (1): 48-53
101. Rothermundt M, Ponath G, Glaser T, et al. S100B serum levels and long-term improvement of negative symptoms in patients with schizophrenia. Neuropsychopharmacology 2004 May; 29 (5): 1004-11
102. Rothermundt M, Falkai P, Ponath G, et al. Glial cell dysfunction in schizophrenia indicated by increased S100B in the CSF. Mol Psychiatry 2004 Oct; 9 (10): 897-9
103. Buka SL, Tsuang MT, Torrey EF, et al. Maternal infections and subsequent psychosis among offspring. Arch Gen Psychiatry 2001 Nov; 58 (11): 1032-7
104. Mortensen PB, Norgaard-Pedersen B, Waltoft BL, et al. Toxoplasma gondii as a risk factor for early-onset schizophrenia: analysis of filter paper blood samples obtained at birth. Biol Psychiatry 2007 Mar 1; 61 (5): 688-93
105. Karlsson H. Viruses and schizophrenia, connection or coincidence. Neuroreport 2003; 14 (4): 535-42
106. Brown AS, Begg MD, Gravenstein S, et al. Serologic evidence of prenatal influenza in the etiology of schizophrenia. Arch Gen Psychiatry 2004 Aug; 61 (8): 774-80
107. Fatemi SH, Reutiman TJ, Folsom TD, et al. The role of cerebellar genes in pathology of autism and schizophrenia. Cerebellum 2007 May 16: 1-16
108. Asp L, Beraki S, Aronsson F, et al. Gene expression changes in brains of mice exposed to a maternal virus infection. Neuroreport 2005 Jul 13; 16 (10): 1111-5
109. Shi L, Fatemi SH, Sidwell RW, et al. Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring. J Neurosci 2003; 23 (1): 297-302
110. Holtze M, Asp L, Schwieler L, et al. Induction of the kynurenine pathway by neurotropic influenza A virus infection. J Neurosci Res 2008 Jul 24; 86 (16): 3674-83
111. Morris RG, Davis S, Butcher SP. Hippocampal synaptic plasticity and NMDA receptors: a role in information storage? Philos Trans R Soc Lond B Biol Sci 1990 Aug 29; 329 (1253): 187-204
112. Oliver MW, Kessler M, Larson J, et al. Glycine site associated with the NMDA receptor modulates long-term potentiation. Synapse 1990; 5 (4): 265-70
113. Ohno M, Yamamoto T, Watanabe S. Intrahippocampal administration of a glycine site antagonist impairs working memory performance of rats. Eur J Pharmacol 1994 Feb 21; 253 (1-2): 183-7
114. Lee I, Kesner RP. Differential contribution of NMDA receptors in hippocampal subregions to spatial working memory. Nat Neurosci 2002 Feb; 5 (2): 162-8
115. Levin ED, Simon BB. Nicotinic acetylcholine involvement in cognitive function in animals. Psychopharmacology (Berl) 1998 Aug; 138 (3-4): 217-30
116. Heyes MP, Saito K, Crowley JS, et al. Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease. Brain 1992 Oct; 115 (Pt 5): 1249-73
117. Atlas A, Gisslen M, Nordin C, et al. Acute psychotic symptoms in HIV-1 infected patients are associated with increased levels of kynurenic acid in cerebrospinal fluid. Brain Behav Immun 2007 Jan; 21 (1): 86-91
118. Schwieler L, Holtze M, Atlas A, et al. Increased levels of kynurenic acid in the central nervous system may account for neuropsychiatric symptoms in patients with tick-borne encephalitis [poster no. 496.4/FF3; online]. 37th Annual Meeting of the Society for Neuroscience; 2007 Nov 3-7; San Diego (CA).Available fromURL: http://www.abstractsonline.com/viewer/?mkey= %7BFF8B70E5%2DB7F9%2D4D07%2DA58A%2DC1068FDE9D25%7D [Accessed 2008 May 13]
119. Baran H, Cairns N, Lubec B, et al. Increased kynurenic acid levels and decreased brain kynurenine aminotransferase I in patients with Down syndrome. Life Sci 1996; 58 (21): 1891-9
120. Chess AC, Simoni MK, Alling TE, et al. Elevations of endogenous kynurenic acid produce spatial working memory deficits. Schizophr Bull 2007 May; 33 (3): 797-804
121. Shepard PD, Joy B, Clerkin L, et al. Micromolar brain levels of kynurenic acid are associated with a disruption of auditory sensory gating in the rat. Neuropsychopharmacology 2003 Aug; 28 (8): 1454-62
122. Silver H, Feldman P, Bilker W, et al. Working memory deficit as a core neuropsychological dysfunction in schizophrenia. Am J Psychiatry 2003 Oct; 160 (10): 1809-16
123. Light GA, Braff DL, Sprock J, et al. Prepulse inhibition of startle is positively associated with higher order cognition in women [poster no. 806.17/W7; online]. 37th Annual Meeting of the Society for Neuroscience; 2007 Nov 3-7; San Diego (CA). Available from URL: http://www.abstractsonline.com/ viewer/?mkey=%7BFF8B70E5%2DB7F9%2D4D07%2DA58A%2DC1068FDE9D25%7D [Accessed 2008 Nov 12]
124. Bergeron R, Wu HQ, Potter MC, et al. Mice with reduced brain kynurenic acid levels have high extracellular glutamate and show enhanced LTP in the hippocampus [poster 807.15/X14; online]. 37th Annual Meeting of the Society for Neuroscience; 2007 Nov 3-7; San Diego (CA). Available from URL: http://www.abstractsonline.com/viewer/?mkey= %7BFF8B70E5%2DB7F9%2D4D07%2DA58A%2DC1068FDE9D25%7D [Accessed 2008 May 13]
125. Potter MC, Elmer GI, Guidetti P, et al. Improved behavioural performance of kynurenine aminotransferrase II-deficient mice in hippocampus-based learning and memory paradigms [poster no. 265.9/FF5; online]. 36th Annual Meeting of the Society for Neuroscience; 2006 Oct 14-18; Atlanta (GA). Available from URL: http://www.abstractsonline.com/viewer/?mkey= %7BD1974E76%2D28AF%2D4C1C%2D8AE8%2D4F73B56247A7%7D [Accessed 2008 May 13]
126. Coyle JT, Tsai G. The NMDA receptor glycine modulatory site: a therapeutic target for improving cognition and reducing negative symptoms in schizophrenia. Psychopharmacology (Berl) 2004 Jun; 174 (1): 32-8
127. Goff DC, Tsai G, Levitt J, et al. A placebo-controlled trial of D-cycloserine added to conventional neuroleptics in patients with schizophrenia. Arch Gen Psychiatry 1999 Jan; 56 (1): 21-7
128. Schwieler L, Erhardt S. Inhibitory action of clozapine on rat ventral tegmental area dopamine neurons following increased levels of endogenous kynurenic acid. Neuropsychopharmacology 2003 Oct; 28 (10): 1770-7
129. Schwieler L, Engberg G, Erhardt S. Clozapine modulates midbrain dopamine neuron firing via interaction with the NMDA receptor complex. Synapse 2004May; 52 (2): 114-22
130. Javitt DC, Duncan L, Balla A, et al. Inhibition of system A-mediated glycine transport in cortical synaptosomes by therapeutic concentrations of clozapine: implications for mechanisms of action. Mol Psychiatry 2005 Mar; 10 (3): 275-87
131. Pellicciari R, Rizzo RC, Costantino G, et al. Modulators of the kynurenine pathway of tryptophan metabolism: synthesis and preliminary biological evaluation of (S)-4-(ethylsulfonyl)benzoylalanine, a potent and selective kynurenine aminotransferase II (KAT II) inhibitor. ChemMedChem 2006 May; 1 (5): 528-31
132. Dijkman U, Engberg G, Grol CJ. Kynurenic acid and schizophrenia: homology modeling of kynurenine aminotransferase II and docking of its natural substrate [poster no. 536.2/KKK9; online]. 37th Annual Meeting of the Society for Neuroscience; 2007 Nov 3-7; San Diego (CA). Available from URL: http://www.abstractsonline.com/viewer/?mkey= %7BFF8B70E5%2DB7F9%2D4D07%2DA58A%2DC1068FDE9D25%7D [Accessed 2008 May 13]
133. Muller N, Riedel M, Scheppach C, et al. Beneficial antipsychotic effects of celecoxib add-on therapy compared to risperidone alone in schizophrenia. Am J Psychiatry 2002 Jun; 159 (6): 1029-34
134. Muller N, Riedel M, Schwarz MJ. Psychotropic effects of COX-2 inhibitors: a possible new approach for the treatment of psychiatric disorders. Pharmacopsychiatry 2004 Nov; 37 (6): 266-9