Glutamatergic antipsychotic drugs: A new dawn in the treatment of schizophrenia?

Therapeutic Advances in Psychopharmacology

Volumn 1, Issue 1, 2011, Pages 5-18

  Stone, James M ^a  

^a HAMMERSMITH HOSPITAL   (United Kingdom)

Author keywords

antipsychotic drugs; glutamate; pharmacology; psychosis; schizophrenia

Indexed keywords

EID: 84997908352     PISSN: 20451253     EISSN: 20451261     Source Type: Journal    
DOI: 10.1177/2045125311400779     Document Type: Review

References (100)

1. Addington J. Addington D. Maticka-Tyndale E. (1991) Cognitive functioning and positive and negative symptoms in schizophrenia. Schizophrenia Res 5: 123–134.
2. Andreasen N.C. (1999) A unitary model of schizophrenia: Bleuler's “fragmented phrene” as schizencephaly. Arch Gen Psychiatry 56: 781–787.
3. Bartha R. Williamson P.C. Drost D.J. Malla A. Carr T.J. Cortese L. et al. (1997) Measurement of glutamate and glutamine in the medial prefrontal cortex of never-treated schizophrenic patients and healthy controls by proton magnetic resonance spectroscopy. Arch Gen Psychiatry 54: 959–965.
4. Bhattacharyya S. Morrison P.D. Fusar-Poli P. Martin-Santos R. Borgwardt S. Winton-Brown T. et al. (2010) Opposite effects of delta-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology. Neuropsychopharmacology 35: 764–774.
5. Bilder R.M. Reiter G. Bates J. Lencz T. Szeszko P. Goldman R.S. et al. (2006) Cognitive development in schizophrenia: follow-back from the first episode. J Clin Exp Neuropsychol 28: 270–282.
6. Block W. Bayer T.A. Tepest R. Traber F. Rietschel M. Muller D.J. et al. (2000) Decreased frontal lobe ratio of N-acetyl aspartate to choline in familial schizophrenia: a proton magnetic resonance spectroscopy study. Neurosci Lett 289: 147–151.
7. Buchanan R.W. Breier A. Kirkpatrick B. Ball P. Carpenter Jr, W.T. (1998) Positive and negative symptom response to clozapine in schizophrenic patients with and without the deficit syndrome. Am J Psychiatry 155: 751–760.
8. Carter K. Dickerson J. Schoepp D.D. Reilly M. Herring N. Williams J. et al. (2004) The mGlu2/3 receptor agonist LY379268 injected into cortex or thalamus decreases neuronal injury in retrosplenial cortex produced by NMDA receptor antagonist MK-801: possible implications for psychosis. Neuropharmacology 47: 1135–1145.
9. Coyle J.T. (2006) Glutamate and schizophrenia: beyond the dopamine hypothesis. Cellular Mol Neurobiol 26: 365–384.
10. Deakin J.F. Lees J. McKie S. Hallak J.E. Williams S.R. Dursun S.M. (2008) Glutamate and the neural basis of the subjective effects of ketamine: a pharmaco-magnetic resonance imaging study. Arch Gen Psychiatry 65: 154–164.
11. Deutsch S.I. Rosse R.B. Billingslea E.N. Bellack A.S. Mastropaolo J. (2002) Topiramate antagonizes MK-801 in an animal model of schizophrenia. Eur J Pharmacol 449: 121–125.
12. Dingledine R. Borges K. Bowie D. Traynelis S.F. (1999) The glutamate receptor ion channels. Pharmacol Rev 51: 7–61.
13. El-Remessy A.B. Tang Y. Zhu G. Matragoon S. Khalifa Y. Liu E.K. et al. (2008) Neuroprotective effects of cannabidiol in endotoxin-induced uveitis: critical role of p38 MAPK activation. Mol Vision 14: 2190–2203.
14. Esposito G. De Filippis D. Maiuri M.C. De Stefano D. Carnuccio R. Iuvone T. (2006) Cannabidiol inhibits inducible nitric oxide synthase protein expression and nitric oxide production in beta-amyloid stimulated PC12 neurons through p38 MAP kinase and NF-kappaB involvement. Neurosci Lett 399: 91–95.
15. Fell M.J. Katner J.S. Johnson B.G. Khilevich A. Schkeryantz J.M. Perry K.W. et al. (2010) Activation of metabotropic glutamate (mGlu)2 receptors suppresses histamine release in limbic brain regions following acute ketamine challenge. Neuropharmacology 58: 632–639.
16. Fell M.J. Perry K.W. Falcone J.F. Johnson B.G. Barth V.N. Rash K.S. et al. (2009) In vitro and in vivo evidence for a lack of interaction with dopamine D2 receptors by the metabotropic glutamate 2/3 receptor agonists 1S,2S,5R,6S-2-aminobicyclo[3.1.0]hexane-2,6-bicaroxylate monohydrate (LY354740) and (-)-2-oxa-4-aminobicyclo[3.1.0] Hexane-4,6-dicarboxylic acid (LY379268). J Pharmacol Exp Therapeutics 331: 1126–1136.
17. Fujita Y. Ishima T. Kunitachi S. Hagiwara H. Zhang L. Iyo M. et al. (2008) Phencyclidine-induced cognitive deficits in mice are improved by subsequent subchronic administration of the antibiotic drug minocycline. Progress Neuro-psychopharmacol Biol Psychiatry 32: 336–339.
18. Fusar-Poli P. Crippa J.A. Bhattacharyya S. Borgwardt S.J. Allen P. Martin-Santos R. et al. (2009) Distinct effects of {delta}9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing. Arch Gen Psychiatry 66: 95–105.
19. Gibbs J.W. III Sombati S. DeLorenzo R.J. Coulter D.A. (2000) Cellular actions of topiramate: blockade of kainate-evoked inward currents in cultured hippocampal neurons. Epilepsia 41(Suppl. 1): S10–S16.
20. Godino Mdel C. Torres M. Sanchez-Prieto J. (2007) CB1 receptors diminish both Ca(2+) influx and glutamate release through two different mechanisms active in distinct populations of cerebrocortical nerve terminals. J Neurochem 101: 1471–1482.
21. Hallak J.E. Dursun S.M. Bosi D.C. de Macedo L.R. Machado-de-Sousa J.P. Abrao J. et al. (2011) The interplay of cannabinoid and NMDA glutamate receptor systems in humans: preliminary evidence of interactive effects of cannabidiol and ketamine in healthy human subjects. Progress Neuro-psychopharmacol Biol psychiatry 35(1): 198–202.
22. Harrison P.J. Weinberger D.R. (2005) Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol Psychiatry 10: 40–68.
23. Hosak L. Libiger J. (2002) Antiepileptic drugs in schizophrenia: a review. Eur Psychiatry 17: 371–378.
24. Javitt D.C. (2001) Management of negative symptoms of schizophrenia. Curr Psychiatry Rep 3: 413–417.
25. Javitt D.C. (2004) Glutamate as a therapeutic target in psychiatric disorders. Mol Psychiatry 9: 984–997, 979.
26. Javitt D.C. (2007) Glutamate and schizophrenia: phencyclidine, N-methyl-D-aspartate receptors, and dopamine–glutamate Interactions. Int Rev Neurobiol 78: 69–108.
27. Johnson M.P. Nisenbaum E.S. Large T.H. Emkey R. Baez M. Kingston A.E. (2004) Allosteric modulators of metabotropic glutamate receptors: lessons learnt from mGlu1, mGlu2 and mGlu5 potentiators and antagonists. Biochem Soc Trans 32: 881–887.
28. Kane J. Honigfeld G. Singer J. Meltzer H. (1988) Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch Gen Psychiatry 45: 789–796.
29. Kapur S. Mamo D. (2003) Half a century of antipsychotics and still a central role for dopamine D2 receptors. Prog Neuropsychopharmacol Biol Psychiatry 27(7): 1081–1090.
30. Karniol I.G. Shirakawa I. Kasinski N. Pfeferman A. Carlini E.A. (1974) Cannabidiol interferes with the effects of delta 9 - tetrahydrocannabinol in man. Eur J Pharmacol 28: 172–177.
31. Kegeles L.S. Shungu D.C. Anjilvel S. Chan S. Ellis S.P. Xanthopoulos E. et al. (2000) Hippocampal pathology in schizophrenia: magnetic resonance imaging and spectroscopy studies. Psychiatry Res 98: 163–175.
32. Kew J.N. Kemp J.A. (2005) Ionotropic and metabotropic glutamate receptor structure and pharmacology. Psychopharmacology 179: 4–29.
33. Kinney G.G. O'Brien J.A. Lemaire W. Burno M. Bickel D.J. Clements M.K. et al. (2005) A novel selective positive allosteric modulator of metabotropic glutamate receptor subtype 5 has in vivo activity and antipsychotic-like effects in rat behavioral models. J Pharmacol Exp Therapeutics 313: 199–206.
34. Kinon B.J. Zhang L. Williams J.E. Osuntokun O.O. Millen B.A. Kollack-Walker S. (2010) Ly2140023 monohydrate: an agonist at the Mglu2/3 receptor for the treatment of schizophrenia. Schizophrenia Res 117: 379–379.
35. Krystal J.H. Perry Jr, E.B. Gueorguieva R. Belger A. Madonick S.H. Abi-Dargham A. et al. (2005) “Comparative and interactive human psychopharmacologic effects of ketamine and amphetamine: implications for glutamatergic and dopaminergic model psychoses and cognitive function”. Arch Gen Psychiatry 62(9): 985–94.
36. Krystal J.H. Karper L.P. Seibyl J.P. Freeman G.K. Delaney R. Bremner J.D. et al. (1994) Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry 51: 199–214.
37. Lane H.Y. Liu Y.C. Huang C.L. Chang Y.C. Liau C.H. Perng C.H. et al. (2008) Sarcosine (N-methylglycine) treatment for acute schizophrenia: a randomized, double-blind study. Biol Psychiatry 63: 9–12.
38. Law A.J. Deakin J.F. (2001) Asymmetrical reductions of hippocampal NMDAR1 glutamate receptor mRNA in the psychoses. Neuroreport 12: 2971–2974.
39. Lecourtier L. Homayoun H. Tamagnan G. Moghaddam B. (2007) Positive allosteric modulation of metabotropic glutamate 5 (mGlu5) receptors reverses N-Methyl-D-aspartate antagonist-induced alteration of neuronal firing in prefrontal cortex. Biol Psychiatry 62: 739–746.
40. Levkovitz Y. Levi U. Braw Y. Cohen H. (2007) Minocycline, a second-generation tetracycline, as a neuroprotective agent in an animal model of schizophrenia. Brain Res 1154: 154–162.
41. Levkovitz Y. Mendlovich S. Riwkes S. Braw Y. Levkovitch-Verbin H. Gal G. et al. (2010) A double-blind, randomized study of minocycline for the treatment of negative and cognitive symptoms in early-phase schizophrenia. J Clin Psychiatry 71: 138–149.
42. Lewis D.A. Cho R.Y. Carter C.S. Eklund K. Forster S. Kelly M.A. et al. (2008) Subunit-selective modulation of GABA type A receptor neurotransmission and cognition in schizophrenia. Am J Psychiatry 165: 1585–1593.
43. Lewis D.A. Hashimoto T. Volk D.W. (2005) Cortical inhibitory neurons and schizophrenia. Nat Rev Neurosci 6: 312–24.
44. Liem-Moolenaar M. Zoethout R.W. de Boer P. Schmidt M. de Kam M.L. Cohen A.F. et al. (2010) The effects of a glycine reuptake inhibitor R231857 on the central nervous system and on scopolamine-induced impairments in cognitive and psychomotor function in healthy subjects. J Psychopharmacol 24: 1681–1687.
45. Lindsley C.W. Wisnoski D.D. Leister W.H. O'brien J.A. Lemaire W. Williams D.L. Jr et al. (2004) Discovery of positive allosteric modulators for the metabotropic glutamate receptor subtype 5 from a series of N-(1,3-diphenyl-1H- pyrazol-5-yl)benzamides that potentiate receptor function in vivo. J Med Chem 47: 5825–5828.
46. Lodge D.J. Grace A.A. (2006) The hippocampus modulates dopamine neuron responsivity by regulating the intensity of phasic neuron activation. Neuropsychopharmacology 31: 1356–61.
47. Long L.E. Malone D.T. Taylor D.A. (2006) Cannabidiol reverses MK-801-induced disruption of prepulse inhibition in mice. Neuropsychopharmacology 31: 795–803.
48. Lorrain D.S. Baccei C.S. Bristow L.J. Anderson J.J. Varney M.A. (2003a) Effects of ketamine and N-methyl-D-aspartate on glutamate and dopamine release in the rat prefrontal cortex: modulation by a group II selective metabotropic glutamate receptor agonist LY379268. Neuroscience 117: 697–706.
49. Lorrain D.S. Schaffhauser H. Campbell U.C. Baccei C.S. Correa L.D. Rowe B. et al. (2003b) Group II mGlu receptor activation suppresses norepinephrine release in the ventral hippocampus and locomotor responses to acute ketamine challenge. Neuropsychopharmacology 28: 1622–1632.
50. Lutkenhoff E.S. van Erp T.G. Thomas M.A. Therman S. Manninen M. et al. (2010) Proton MRS in twin pairs discordant for schizophrenia. Mol Psychiatry 15(3): 308–318.
51. Martina M. Gorfinkel Y. Halman S. Lowe J.A. Periyalwar P. Schmidt C.J. et al. (2004) Glycine transporter type 1 blockade changes NMDA receptor-mediated responses and LTP in hippocampal CA1 pyramidal cells by altering extracellular glycine levels. J Physiol 557: 489–500.
52. McEvoy J.P. Lieberman J.A. Stroup T.S. Davis S.M. Meltzer H.Y. Rosenheck R.A. for the CATIE Investigators. et al. (2006) Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Am J Psychiatry 163: 600–610.
53. Meltzer H.Y. Arvanitis L. Bauer D. Rein W. for the Meta-Trial Study Group. (2004) Placebo-controlled evaluation of four novel compounds for the treatment of schizophrenia and schizoaffective disorder. Am J Psychiatry 161: 975–984.
54. Moghaddam B. (2004) Targeting metabotropic glutamate receptors for treatment of the cognitive symptoms of schizophrenia. Psychopharmacology (Berl) 174: 39–44.
55. Moghaddam B. Adams B. Verma A. Daly D. (1997) Activation of glutamatergic neurotransmission by ketamine: a novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex. J Neurosci 17: 2921–2927.
56. Moreira F.A. Guimaraes F.S. (2005) Cannabidiol inhibits the hyperlocomotion induced by psychotomimetic drugs in mice. Eur J Pharmacol 512: 199–205.
57. Morgan C.J. Curran H.V. (2006) Acute and chronic effects of ketamine upon human memory: a review. Psychopharmacology 188: 408–424.
58. Morgan C.J. Curran H.V. (2008) Effects of cannabidiol on schizophrenia-like symptoms in people who use cannabis. Br J Psychiatry 192: 306–307.
59. Morgan C.J. Schafer G. Freeman T.P. Curran H.V. (2010) Impact of cannabidiol on the acute memory and psychotomimetic effects of smoked cannabis: naturalistic study. Br J Psychiatry 197: 285–290.
60. Neu A. Foldy C. Soltesz I. (2007) Postsynaptic origin of CB1-dependent tonic inhibition of GABA release at cholecystokinin-positive basket cell to pyramidal cell synapses in the CA1 region of the rat hippocampus. J Physiol 578: 233–247.
61. Ohrmann P. Siegmund A. Suslow T. Spitzberg K. Kersting A. Arolt V. et al. (2005) Evidence for glutamatergic neuronal dysfunction in the prefrontal cortex in chronic but not in first-episode patients with schizophrenia: a proton magnetic resonance spectroscopy study. Schizophr Res 73: 153–157.
62. Olney J.W. Farber N.B. (1995) Glutamate receptor dysfunction and schizophrenia. Arch Gen Psychiatry 52: 998–1007.
63. Olney J.W. Newcomer J.W. Farber N.B. (1999) NMDA receptor hypofunction model of schizophrenia. J Psychiatr Res 33: 523–533.
64. Ongur D. Prescot A.P. Jensen J.E. Cohen B.M. Renshaw P.F. (2009) Creatine abnormalities in schizophrenia and bipolar disorder. Psychiatry Res 172: 44–48.
65. Patil S.T. Zhang L. Martenyi F. Lowe S.L. Jackson K.A. Andreev B.V. et al. (2007) Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial. Nat Med 13: 1102–1107.
66. Perry K.W. Falcone J.F. Fell M.J. Ryder J.W. Yu H. Love P.L. et al. (2008) Neurochemical and behavioral profiling of the selective GlyT1 inhibitors ALX5407 and LY2365109 indicate a preferential action in caudal vs. cortical brain areas. Neuropharmacology 55: 743–754.
67. Phillips L.J. Yung A.R. McGorry P.D. (2000) Identification of young people at risk of psychosis: validation of Personal Assessment and Crisis Evaluation Clinic intake criteria. Aust N Z J Psychiatry 34(Suppl): S164–S169.
68. Pi R. Li W. Lee N.T. Chan H.H. Pu Y. Chan L.N. et al. (2004) Minocycline prevents glutamate-induced apoptosis of cerebellar granule neurons by differential regulation of p38 and Akt pathways. J Neurochem 91: 1219–1230.
69. Pilowsky L.S. Bressan R.A. Stone J.M. Erlandsson K. Mulligan R.S. Krystal J.H. et al. (2006) First in vivo evidence of an NMDA receptor deficit in medication-free schizophrenic patients. Mol Psychiatry 11: 118–119.
70. Pinard E. Alanine A. Alberati D. Bender M. Borroni E. Bourdeaux P. et al. (2010) Selective GlyT1 inhibitors: discovery of [4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl][5-methanesulfon yl-2-((S)-2,2,2-trifluoro-1-methylethoxy)phenyl]methanone (RG1678), a promising novel medicine to treat schizophrenia. J Medicinal Chem 53: 4603–4614.
71. Rothman D.L. Behar K.L. Hyder F. Shulman R.G. (2003) In vivo NMR studies of the glutamate neurotransmitter flux and neuroenergetics: implications for brain function. Annu Rev Physiol 65: 401–427.
72. Rowland L.M. Spieker E.A. Francis A. Barker P.B. Carpenter W.T. Buchanan R.W. (2009) White matter alterations in deficit schizophrenia. Neuropsychopharmacology 34: 1514–1522.
73. Schwieler L. Linderholm K.R. Nilsson-Todd L.K. Erhardt S. Engberg G. (2008) Clozapine interacts with the glycine site of the NMDA receptor: electrophysiological studies of dopamine neurons in the rat ventral tegmental area. Life Sci 83: 170–175.
74. Seeman P. Battaglia G. Corti C. Corsi M. Bruno V. (2009) Glutamate receptor mGlu2 and mGlu3 knockout striata are dopamine supersensitive, with elevated D2(High) receptors and marked supersensitivity to the dopamine agonist (+)PHNO. Synapse 63: 247–251.
75. Seeman P. Guan H.C. (2009) Glutamate agonist LY404,039 for treating schizophrenia has affinity for the dopamine D2(High) receptor. Synapse 63: 935–939.
76. Seeman P. Lee T. (1975) Antipsychotic drugs: direct correlation between clinical potency and presynaptic action on dopamine neurons. Science 188: 1217–1219.
77. Sharp F.R. Tomitaka M. Bernaudin M. Tomitaka S. (2001) Psychosis: pathological activation of limbic thalamocortical circuits by psychomimetics and schizophrenia? Trends Neurosci 24: 330–334.
78. Stefani M.R. 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.
79. Stone J.M. (2009) Imaging the glutamate system in humans: relevance to drug discovery for schizophrenia. Curr Pharmaceut Design 15: 2594–2602.
80. Stone J.M. Day F. Tsagaraki H. Valli I. McLean M.A. Lythgoe D.J. et al. (2009) Glutamate dysfunction in people with prodromal symptoms of psychosis: relationship to gray matter volume. Biol Psychiatry 66: 533–539.
81. Stone J.M. Erlandsson K. Arstad E. Squassante L. Teneggi V. Bressan R.A. et al. (2008) Relationship between ketamine-induced psychotic symptoms and NMDA receptor occupancy: a [(123)I]CNS-1261 SPET study. Psychopharmacology (Berl) 197: 401–408.
82. Stone J.M. Howes O.D. Egerton A. Kambeitz J. Allen P. Lythgoe D.J. et al. (2010a) Altered relationship between hippocampal glutamate levels and striatal dopamine function in subjects at ultra high risk of psychosis. Biol Psychiatry 68: 599–602.
83. Stone J.M. Morrison P.D. Pilowsky L.S. (2007) Glutamate and dopamine dysregulation in schizophrenia—a synthesis and selective review. J Psychopharmacol 21: 440–452.
84. Stone J.M. Raffin M. Morrison P. McGuire P.K. (2010b) Review: The biological basis of antipsychotic response in schizophrenia. J Psychopharmacol 24: 953–964.
85. Tamminga C.A. Buchanan R.W. Gold J.M. (1998) The role of negative symptoms and cognitive dysfunction in schizophrenia outcome. Int Clin Psychopharmacol 13(Suppl. 3): S21–S26.
86. Tayoshi S. Sumitani S. Taniguchi K. Shibuya-Tayoshi S. Numata S. Iga J. et al. (2009) Metabolite changes and gender differences in schizophrenia using 3-Tesla proton magnetic resonance spectroscopy (1H-MRS). Schizophrenia Res 108: 69–77.
87. Théberge J. Al-Semaan Y. Williamson P.C. Menon R.S. Neufeld R.W.J. Rajakumar N. et al. (2003) Glutamate and glutamine in the anterior cingulate and thalamus of medicated patients with chronic schizophrenia and healthy comparison subjects measured with 4.0-T proton MRS. Am J Psychiatry 160: 2231–2233.
88. Théberge J. Bartha R. Drost D.J. Menon R.S. Malla A. Takhar J. et al. (2002) Glutamate and glutamine measured with 4.0 T proton MRS in never-treated patients with schizophrenia and healthy volunteers. Am J Psychiatry 159: 1944–1946.
89. Tibbo P. Hanstock C. Valiakalayil A. Allen P. (2004) 3-T proton MRS investigation of glutamate and glutamine in adolescents at high genetic risk for schizophrenia. Am J Psychiatry 161: 1116–1118.
90. Tiihonen J. Halonen P. Wahlbeck K. Repo-Tiihonen E. Hyvarinen S. Eronen M. et al. (2005) Topiramate add-on in treatment-resistant schizophrenia: a randomized, double-blind, placebo-controlled, crossover trial. J Clin Psychiatry 66: 1012–1015.
91. Tiihonen J. Wahlbeck K. Kiviniemi V. (2009) The efficacy of lamotrigine in clozapine-resistant schizophrenia: a systematic review and meta-analysis. Schizophrenia Res 109: 10–14.
92. Tsai G.E. Lin P.Y. (2010) Strategies to enhance N-methyl-D-aspartate receptor-mediated neurotransmission in schizophrenia, a critical review and meta-analysis. Curr Pharm Des 16(5): 522–537.
93. Uslaner J.M. Parmentier-Batteur S. Flick R.B. Surles N.O. Lam J.S. McNaughton C.H. et al. (2009) Dose-dependent effect of CDPPB, the mGluR5 positive allosteric modulator, on recognition memory is associated with GluR1 and CREB phosphorylation in the prefrontal cortex and hippocampus. Neuropharmacology 57: 531–538.
94. Vales K. Svoboda J. Benkovicova K. Bubenikova-Valesova V. Stuchlik A. (2010) The difference in effect of mGlu2/3 and mGlu5 receptor agonists on cognitive impairment induced by MK-801. Eur J Pharmacol 639: 91–98.
95. Vardigan J.D. Huszar S.L. McNaughton C.H. Hutson P.H. Uslaner J.M. (2010) MK-801 produces a deficit in sucrose preference that is reversed by clozapine, D-serine, and the metabotropic glutamate 5 receptor positive allosteric modulator CDPPB: relevance to negative symptoms associated with schizophrenia? Pharmacol Biochem Behavior 95: 223–229.
96. Ventura J. Hellemann G.S. Thames A.D. Koellner V. Nuechterlein K.H. (2009) Symptoms as mediators of the relationship between neurocognition and functional outcome in schizophrenia: a meta-analysis. Schizophrenia Res 113: 189–199.
97. Wilkins A. Nikodemova M. Compston A. Duncan I. (2004) Minocycline attenuates nitric oxide-mediated neuronal and axonal destruction in vitro. Neuron Glia Biol 1: 297–305.
98. Williams J.B. Mallorga P.J. Jeffrey Conn P. Pettibone D.J. Sur C. (2004) Effects of typical and atypical antipsychotics on human glycine transporters. Schizophr Res 71(1): 103–112.
99. Zhang L. Shirayama Y. Iyo M. Hashimoto K. (2007) Minocycline attenuates hyperlocomotion and prepulse inhibition deficits in mice after administration of the NMDA receptor antagonist dizocilpine. Neuropsychopharmacology 32: 2004–2010.
100. Zuardi A.W. Crippa J.A. Hallak J.E. Moreira F.A. Guimaraes F.S. (2006) Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug. Braz J Med Biol Res 39: 421–429.