Acute elevations of brain kynurenic acid impair cognitive flexibility: Normalization by the alpha7 positive modulator galantamine

Psychopharmacology

Volumn 220, Issue 3, 2012, Pages 627-637

  Alexander, Kathleen S ^a   Wu, Hui Qiu ^b   Schwarcz, Robert ^b   Bruno, John P ^a  

^a OHIO STATE UNIVERSITY   (United States)

^b MARYLAND PSYCHIATRIC RESEARCH CENTER   (United States)

Author keywords

Animal model; Cognition; Glutamate; Kynurenine; Schizophrenia

Indexed keywords

GALANTAMINE; GLUTAMIC ACID; KYNURENIC ACID; KYNURENINE;

ALLOSTERISM; ANIMAL BEHAVIOR; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; ATTENTION; BRAIN LEVEL; COGNITIVE DEFECT; CONTROLLED STUDY; DOWN REGULATION; DRUG EFFECT; DRUG MECHANISM; EXECUTIVE FUNCTION; MALE; MENTAL TASK; MICRODIALYSIS; NONHUMAN; OLFACTORY DISCRIMINATION; PREFRONTAL CORTEX; PRIORITY JOURNAL; RAT; TACTILE DISCRIMINATION; TASK PERFORMANCE; UPREGULATION; VALIDATION PROCESS;

ANIMALS; BRAIN; COGNITION; COGNITION DISORDERS; DISEASE MODELS, ANIMAL; GALANTAMINE; GLUTAMIC ACID; KYNURENIC ACID; KYNURENINE; MALE; NOOTROPIC AGENTS; PREFRONTAL CORTEX; RATS; RATS, WISTAR; RECEPTORS, NICOTINIC; SCHIZOPHRENIA;

EID: 84858445314     PISSN: 00333158     EISSN: 14322072     Source Type: Journal    
DOI: 10.1007/s00213-011-2539-2     Document Type: Article

References (89)

1. Barnett JH, Robbins TW, Leeson VC, Sahakian BJ, Joyce EM, Blackwell AD (2010) Assessing cognitive function in clinical trials of schizophrenia. Neurosci Biobehav Rev 34:1161-1177
2. Bauer D, Gupta D, Haroutunian V, Meador-Woodruff JH, Mccullumsmith RE (2008) Abnormal expression of glutamate transporter and transporter interacting molecules in prefrontal cortex in elderly patients with schizophrenia. Schizophr Res 104:108-120
3. Baune BT, Suslow T, Beste C, Birosova E, Domschke K, Sehlmeyer C, Konrad C (2010) Association between genetic variants of the metabotropic glutamate receptor 3 (GRM3) and cognitive set shifting in healthy individuals. Genes Brain Behav 9:459-466
4. Birrell J, Brown V (2000) Medial frontal cortex mediates perceptual attentional set shifting in the rat. J Neurosci 20:4320-4324 (Pubitemid 30365702)
5. Brooks JM, Thomsen MS, Mikkelsen JD, Sarter M, Bruno JP (2010) Attentional set-shifting deficits in a neurodevelopmental animal model of schizophrenia-reversal with an alpha7 nAChR agonist. 368.08. 2010 Neuroscience Meeting Planner. Society for Neuroscience, San Diego, Online
6. Buchanan RW, Conley RR, Dickinson D, Ball MP, Feldman S, Gold JM, McMahon RP (2008) Galantamine for the treatment of cognitive impairments in people with schizophrenia. Am J Psychiat 165:82-89 (Pubitemid 351704556)
7. Cabrera SM, Chavez CM, Corley SR, Kitto MR, Butt AE (2006) Selective lesions of the nucleus basalis magnocellularis impair cognitive flexibility. Behav Neurosci 120:298-306 (Pubitemid 43807379)
8. Chen EY, Tam DK, Dunn EL, Miao MY, Yeung WS, Wong CK, Chan WF, Tang WN (2005) Neurocognitive and clinical predictors for vocational outcome following first episode schizophrenia: a 3 year prospective study. Schizophr Bull 31:320
9. Chess AC, Simoni MK, Alling TE, Bucci DJ (2007) Elevations of endogenous kynurenic acid produce spatial working memory deficits. Schizophr Bull 33:797-804 (Pubitemid 47343705)
10. Chess AC, Landers AM, Bucci DJ (2009) L-Kynurenine treatment alters contextual fear conditioning and context discrimination but not cue-specific fear conditioning. Behav Brain Res 201:325-331
11. Dalley JW, Cardinal RN, Robbins TW (2004) Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates. Neurosci Biobehav Rev 28:771-784 (Pubitemid 39535871)
12. Dalton GL, Ma LM, Phillips AG, Floresco SB (2011) Blockade of NMDA GluN2B receptors selectively impairs behavioral flexibility but not initial discrimination learning. Psychopharmacology 216:525-535
13. Darrah JM, Stefani MR, Moghaddam B (2008) Interaction of N-methyl-D-aspartate and group 5 metabotropic glutamate receptors on behavioral flexibility using a novel operant set-shift paradigm. Behav Pharmacol 19:225-234 (Pubitemid 351670403)
14. Dias R, Robbins TW, Roberts AC (1996) Dissociation in prefrontal cortex of affective and attentional shifts. Nature 380:69-72 (Pubitemid 26076238)
15. Egerton A, Reid L, McKerchar CE, Morris BJ, Pratt JA (2005) Impairment in perceptual attentional set-shifting following PCP administration: a rodent model of set-shifting deficits in schizophrenia. Psychopharmacology 179:77-84 (Pubitemid 40576694)
16. Erhardt S, Blennow K, Nordin C, Skogh E, Lindström LH, Engberg G (2001) Kynurenic acid levels are elevated in the cerebrospinal fluid of patients with schizophrenia. Neurosci Lett 313:96-98 (Pubitemid 32973903)
17. Erhardt S, Schwieler L, Emanuelsson C, Geyer M (2004) Endogenous kynurenic acid disrupts prepulse inhibition. Biol Psychiat 56:255-260 (Pubitemid 39092940)
18. Floresco SB, Magyar O, Ghods-Sharifi S, Vexelman C, Tse MT (2006) Multiple dopaminergic receptor subtypes in the medial prefrontal cortex of the rat regulate set-shifting. Neuropsycho-pharmacology 31:297-309 (Pubitemid 43113395)
19. Floresco SB, Zhang Y, Enomoto T (2009) Neural circuits subserving behavioral flexibility and their relevance to schizophrenia. Behav Brain Res 204:396-409
20. Gal EM, Sherman AD (1980) L-Kynurenine: its synthesis and possible regulatory function in brain. Neurochem Res 5:223-239 (Pubitemid 10134133)
21. Ghods-Sharifi S, Haluk DM, Floresco SB (2008) Differential effects of inactivation of the orbitofrontal cortex on strategy set-shifting and reversal learning. Neurobiol Learning Mem 89:567-573 (Pubitemid 351484252)
22. Gold JM (2004) Cognitive deficits as treatment targets in schizophrenia. Schizophr Res 72:21-28 (Pubitemid 39452902)
23. Gonzalez-Burgos G, Hashimoto T, Lewis DA (2010) Alterations of cortical GABA neurons and network oscillations in schizophrenia. Curr Psychiat Rep 12:335-344
24. Goto Y, Yang CR, Otani S (2010) Functional and dysfunctional synaptic plasticity in prefrontal cortex: roles in psychiatric disorders. Biol Psychiat 67:199-207
25. Gruber AJ, Calhoon GG, Shusterman I, Schoenbaum G, Roesch MR, O'Donnell P (2010) More is less: a disinhibited prefrontal cortex impairs cognitive flexibility. J Neurosci 30:17102-17110
26. Guidetti P, Hoffman GE, Melendez-Ferro M, Albuquerque EX, Schwarcz R (2007) Astrocytic localization of kynurenine aminotransferase II in the rat brain visualized by immunocytochemistry. Glia 55:78-92 (Pubitemid 44845511)
27. Guillin O, Abi-Dargham A, Laruelle M (2007) Neurobiology of dopamine in schizophrenia. Int Rev Neurobiol 78:1-9
28. Haluk DM, Floresco SB (2009) Ventral striatal dopamine modulation of different forms of behavioral flexibility. Neuropsychopharmacology 34:2041-2052
29. Heinrichs RW (2005) The primacy of cognition in schizophrenia. Am Psychol 60:229-242
30. Hilmas C, Pereira EF, Alkondon M, Rassoulpour A, Schwarcz R, Albuquerque EX (2001) The brain metabolite kynurenic acid inhibits alpha7 nicotinic receptor activity and increases non-alpha7 nicotinic expression: physiopathological implications. J Neurosci 21:7463-7473 (Pubitemid 32904945)
31. Hyde TM, Crook JM (2001) Cholinergic systems and schizophrenia: primary pathology or epiphenomena? J Chem Neuroanat 22:53-63 (Pubitemid 32695509)
32. Javitt DC (2007) Glutamate and schizophrenia: phencyclidine, N-methyl-D-aspartate receptors, and dopamine-glutamate interactions. Int Rev Neurobiol 78:69-108
33. Keefe RSE (2007) Cognitive deficits in patients with schizophrenia: effects and treatment. J Clin Psychiat 68:8-13
34. Kehagia AA, Murray GK, Robbins TW (2010) Learning and cognitive flexibility: frontostriatal function and monoaminergic modulation. Curr Opin Neurobiol 20:199-204
35. Kerns JG, Nuechterlein KH, Braver TS, Barch DM (2008) Executive functioning component mechanisms and schizophrenia. Biol Psychiat 64:26-33 (Pubitemid 351783247)
36. Konradsson-Geuken Å, Gash CR, Alexander KA, Pomerleu F, Huettl P, Gerhardt GA, Bruno JP (2009) Second-by-second analysis of alpha7 nicotine receptor regulation of glutamate release in the prefrontal cortex of awake rats. Synapse 63:1069-1082
37. Konradsson-Geuken Å, Wu HQ, Gash CR, Alexander KS, Campbell A, Sozeri Y, Pellicciari R, Schwarcz R, Bruno JP (2010) Cortical kynurenic acid bi-directionally modulates prefrontal glutamate levels as assessed by microdialysis and rapid electrochemistry. Neuroscience 169:1848-1859
38. Krystal JH, D'Souza DC, Petrakis IL, Belger A, Berman RM, Charney DS, Abi-Saab W, Madonick S (1999) NMDA agonists and antagonists as probes of glutamatergic dysfunction and pharmacotherapies in neuropsychiatric disorders. Harv Rev Psychiat 7:125-143 (Pubitemid 30240826)
39. Lie CH, Specht K, Marshall JC, Fink GR (2006) Using fMRI to decompose the neural processes underlying the Wisconsin Card Sorting Test. NeuroImage 30:1038-1049
40. Lilienfeld S (2002) Galantamine - a novel cholinergic drug with a unique dual mode of action for the treatment of patients with Alzheimer's disease. CNS Drug Rev 8:159-176 (Pubitemid 34874383)
41. Lindenmayer JP, Khan A (2011) Galantamine augmentation of long-acting injectable risperidone for cognitive impairments in chronic schizophrenia. Schizophr Res 125:267-277
42. Livingstone PD, Dickinson JA, Srinivasan J, Kew JN, Wonnacott S (2010) Glutamate-dopamine crosstalk in the rat prefrontal cortex is modulated by alpha7 nicotinic receptors and potentiated by PNU-120596. J Mol Med 40:171-176
43. Lopes C, Pereira EFR, Wu HQ, Pranik P, Njar V, Schwarcz R, Albuquerque EX (2007) Competitive antagonism between the nicotinic allosteric potentiating ligand galantamine and kynurenic acid at α7* nicotinic receptors. J Pharmacol Exp Ther 322:48-58 (Pubitemid 46956368)
44. Mathew SV, Law AJ, Lipska BK, Davila-Garcia MI, Zamora ED, Mitkus SN, Vakkalanka R, Straub RE, Weinberger DR, Kleinman JE, Hyde TM (2007) Alpha 7 nicotinic acetylcholine receptor mRNA expression and binding in postmortem human brain are associated with genetic variation in neuregulin 1. Hum Mol Gen 16:2921-2932 (Pubitemid 350048389)
45. McAlonan K, Brown VJ (2003) Orbital prefrontal cortex mediates reversal learning and not attentional set shifting in the rat. Behav Brain Res 146:97-103 (Pubitemid 37476137)
46. McGaughy J, Ross RS, Eichenbaum H (2008) Noradrenergic, but not cholinergic, deafferentation of prefrontal cortex impairs atten-tional set-shifting. Neuroscience 153:63-71
47. Miller CL, Llenos IC, Dulay JR, Barillo MM, Yolken RH, Weis S (2004) Expression of the kynurenine pathway enzyme tryptophan 2,3-dioxygenase is increased in the frontal cortex of individuals with schizophrenia. Neurobiol Dis 15:618-629 (Pubitemid 38429977)
48. Miller CL, Llenos IC, Dulay JR, Weis S (2006) Upregulation of the initiating step of the kynurenine pathway in postmortem anterior cingulate cortex from individuals with schizophrenia and bipolar disorder. Brain Res 1073-1074:25-37
49. Nilsson LK, Linderholm KR, Erhardt S (2006) Subchronic treatment with kynurenine and probenecid: effects on prepulse inhibition and firing of midbrain dopamine neurons. J Neural Transm 113:557-571 (Pubitemid 43673596)
50. Nuechterlein KH, Barch DM, Gold JM, Goldberg TE, Green MF, Heaton RK (2004) Identification of separable cognitive factors in schizophrenia. Schizophr Res 72:29-39 (Pubitemid 39452903)
51. Nuechterlein KH, Luck SJ, Lustig C, Sarter M (2009) CNTRICS final task selection: control of attention. Schizophr Bull 35:182-196
52. Olincy A, Harris JG, Johnson LL, Pender V, Kongs S, Allensworth D, Ellis J, Zerbe GO, Leonard S, Stevens KE, Stevens JO, Martin L, Adler LE, Soti F, Kern WR, Freedman R (2006) Proof-of concept trial of an alpha7 nicotinic agonist in schizophrenia. Arch Gen Psychiat 63:630-638 (Pubitemid 43848294)
53. Pantelis C, Barber FZ, Barnes TR, Nelson HE, Owen AM, Robbins TW (1999) Comparison of set-shifting ability in patients with chronic schizophrenia and frontal lobe damage. Schizophr Res 37:251-270 (Pubitemid 29298095)
54. Parikh V, Sarter M (2008) Cholinergic mediation of attention- contributions of phasic and tonic increases in prefrontal cholinergic activity. Ann NYAcad Sci 1129:225-235 (Pubitemid 351990291)
55. Pedersen CS, Goetghebeur P, Dias R (2009) Chronic infusion of PCP via osmotic mini- pumps: a new rodent model of cognitive deficit in schizophrenia characterized by impaired attentional set-shifting (ID/ED) performance. J Neurosci Meth 185:66-69
56. Pocivavsek A, Wu H-Q, Potter MC, Elmer GI, Pellicciari R, Schwarcz R (2011) Fluctuations in endogenous kynurenic acid control hippocampal glutamate and memory. Neuropsychopharmacology 36:2357-2367
57. Potkin SG, Fleming K, Jin Y, Gulasekaram B (2001) Clozapine enhances neurocognition and clinical symptomatology more than standard neuroleptics. J Clin Psychopharm 21:479-483 (Pubitemid 32937429)
58. Prouteau A, Verdoux N, Briand C, Lesage A, Lalonde P, Nicole L, Reinharz D, Stip E (2005) Cognitive predictors of psychosocial functioning outcome in schizophrenia: a follow-up study of subjects participating in a rehabilitation program. Schizophr Res 77:343-353 (Pubitemid 41112227)
59. Ragozzino ME, Wilcox C, Raso M, Kesner RP (1999) Involvement of rodent prefrontal cortex subregions in strategy switching. Behav Neurosci 113:32-41 (Pubitemid 29138445)
60. Ragozzino ME, Ragozzino KE, Mizumori SJY, Kesner RP (2002) The role of the dorsomedial striatum in behavioral flexibility for response and visual cue discrimination learning. Behav Neurosci 116:105-115 (Pubitemid 34094571)
61. Rassoulpour A, Wu H-Q, Ferré S, Schwarcz R (2005) Nanomolar concentrations of kynurenic acid reduce extracellular dopamine levels in the striatum. J Neurochem 93:762-765 (Pubitemid 40617635)
62. Robbins TW (2007) Shifting and stopping: fronto-striatal substrates, neurochemical modulation and clinical implications. Philos Trans Roy Soc B 362:917-932 (Pubitemid 47056819)
63. Robbins TW, Arnsten AFT (2009) The neuropsychopharmacology of fronto-executive function: monoaminergic modulation. Annu Rev Neurosci 32:267-287
64. Robbins TW, Roberts AC (2007) Differential regulation of fronto-executive function by the monoamines and acetylcholine. Cereb Cortex 17:151-160
65. Rollnik JD, Borsutzky M, Huber TJ, Mogk H, Seifert J, Emrich HM, Schneider U (2002) Short-term cognitive improvement in schizophrenics treated with typical and atypical neuroleptics. Neuropsychobiology 45:74-80 (Pubitemid 34224981)
66. Rygula R, Walker SC, Clarke HF, Robbins TW, Roberts AC (2010) Differential contributions of the primate ventrolateral prefrontal and orbitofrontal cortex to serial reversal learning. J Neurosci 30:14552-14559
67. Sathyasaikumar KV, Stachowski EK, Wonodi I, Robers RC, Rassoulpour A, McMahon RP, Schwarcz R (2010). Impaired kynurenine pathway metabolism in the prefrontal cortex of individuals with schizophrenia. Schizophrenia Bulletin (in press)
68. Scarr E, Cowie TF, Kanellakis S, Sundram S, Pantelis C, Dean B (2009) Decreased cortical muscarinic receptors define a subgroup of subjects with schizophrenia. Mol Psychiatr 14:1017-1023
69. Schubert MH, Young KA, Hicks PB (2006) Galantamine improves cognition in schizophrenic patients stabilized on risperidone. Biol Psychiat 60:530-533 (Pubitemid 44402376)
70. Schwarcz R, Rassoulpour A, Wu H-Q, Medoff D, Tamminga CA, Roberts RC (2001) Increased cortical kynurenate content in schizophrenia. Biol Psychiat 50:521-530 (Pubitemid 32971883)
71. Shank RP, Leo GC, Zielke HR (1993) Cerebral metabolic compart-mentation as revealed by nuclear magnetic resonance analysis of D-[1-13C]glucose metabolism. J Neurochem 61:315-323 (Pubitemid 23175916)
72. Shepard PD, Joy B, Clerkin L, Schwarcz R (2003) Micromolar brain levels of kynurenic acid are associated with a disruption of auditory sensory gating in the rat. Neuropsychopharmacology 28:1454-1462 (Pubitemid 41070880)
73. Shigeta M, Homma A (2001) Donepezil for Alzheimer's disease: pharmacodynamic, pharmacokinetic, and clinical profiles. CNS Drug Rev 7:353-368 (Pubitemid 34263871)
74. Speciale C, Hares K, Schwarcz R, Brookes N (1989) High-affinity uptake of L-kynurenine by a Na#sup#+#/sup#-independent transporter of neutral amino acids in astrocytes. J Neurosci 9:2066-2072 (Pubitemid 19156993)
75. Stefani MR, Moghaddam B (2005) Systemic and prefrontal cortical NMDA receptor blockade differentially affect discrimination learning and set-shift ability in rats. Behav Neurosci 119:420-428 (Pubitemid 40547947)
76. Stefani MR, Moghaddam B (2010) Activation of type 5 metabotropic glutamate receptors attenuates deficits in cognitive flexibility induced by NMDA receptor blockade. Eur J Pharmacol 639:26-32
77. Stefani MR, Groth K, Moghaddam B (2003) Glutamate receptors in the rat medial prefrontal cortex regulate set-shifting ability. Behav Neurosci 117:728-737 (Pubitemid 36935384)
78. Swartz KJ, During MJ, Freese A, Beal MF (1990) Cerebral synthesis and release of kynurenic acid: an endogenous antagonist of excitatory amino acid receptors. J Neurosci 10:2965-2973
79. Tait DS, Brown VJ (2008) Lesions of the basal forebrain impair reversal learning but not shifting of attentional set in rats. Behav Brain Res 187:100-108 (Pubitemid 350216193)
80. Vasey MW, Thayer JF (1987) The continuing problem of false positives in repeated measures ANOVA in psychophysiology-a multivariate solution. Psychophysiology 24:479-489
81. Volk DW, Lewis DA (2010) Prefrontal cortical circuits in schizophrenia. Curr Top Behav Neurosci 4:485-508
82. Volk DW, Eggan SM, Lewis DA (2010) Alterations in metabotropic glutamate receptor 1 alpha and regulator of G protein signaling 4 in the prefrontal cortex in schizophrenia. Am J Psychiat 167:1489-1498
83. Winterer G, Weinberger DR (2004) Genes, dopamine, and cortical signal-to-noise ratio in schizophrenia. Trends Neurosci 27:683-690 (Pubitemid 39335839)
84. Wonodi I, Schwarcz R (2010) Cortical kynurenine pathway metabolism: a novel target for cognitive enhancement in schizophrenia. Schizophr Bull 36:211-218
85. Wonodi I, Stine OC, Sathyasaikumar KV, Roberts RC, Mitchell BD, Hong LE, Kajii Y, Thaker GK, Schwarcz R (2011) Down-regulated kynurenine 3-monooxygenase gene expression and enzyme activity in schizophrenia and genetic association with schizophrenia endophenotypes. Arch Gen Psychiatr 68:665-674
86. Woo TUW, Shrestha K, Lamb D, Minns MM, Benes FM (2008) N-methyl-D-aspartate receptor and calbinding-containing neurons in the anterior cingulate cortex in schizophrenia and bipolar disorder. Biol Psychiat 64:803-809
87. Wu H-Q, Pelliciari R, Schwarcz R (2006) Bidirectional regulation of extracellular dopamine by endogenous kynurenic acid in the rat medial prefrontal cortex. Soc Neurosci Abst 32:624.3
88. Wu H-Q, Pereira EFR, Bruno JP, Pellicciari R, Albuquerque EX, Schwarcz R (2010) The astrocyte-derived alpha7 nicotonic receptor antagonist kynurenic acid controls extracellular glutamate levels in prefrontal cortex. J Mol Neurosci 40:204-210
89. Zmarowski A, Wu H-Q, Brooks JM, Potter MC, Pellicciari R, Schwarcz R, Bruno JP (2009) Astrocyte-derived kynurenic acid modulates basal and evoked cortical acetylcholine release. Eur J Neurosci 29:529-538