Modeling resilience to schizophrenia in genetically modified mice: a novel approach to drug discovery

References

• Insel TR. Rethinking schizophrenia. Nature 468(7321), 187–193 (2010).
   PubMed Web of Science ®Google Scholar
• Karam CS, Ballon JS, Bivens NM et al. Signaling pathways in schizophrenia: emerging targets and therapeutic strategies. Trends Pharmacol. Sci. 31(8), 381–390 (2010).
   PubMed Web of Science ®Google Scholar
• Lupski JR. Schizophrenia: incriminating genomic evidence. Nature 455(7210), 178–179 (2008).
   PubMed Web of Science ®Google Scholar
• Owen MJ, Craddock N, O’Donovan MC. Suggestion of roles for both common and rare risk variants in genome-wide studies of schizophrenia. Arch. Gen. Psychiatr. 67(7), 667–673 (2010).
   PubMedGoogle Scholar
• Meyer-Lindenberg A. From maps to mechanisms through neuroimaging of schizophrenia. Nature 468(7321), 194–202 (2010).
   PubMed Web of Science ®Google Scholar
• Fatemi SH, Folsom TD. The neurodevelopmental hypothesis of schizophrenia, revisited. Schizophr. Bull. 35(3), 528–548 (2009).
   PubMed Web of Science ®Google Scholar
• Oliveira JM. Nature and cause of mitochondrial dysfunction in Huntington’s disease: focusing on huntingtin and the striatum. J. Neurochem. 114(1), 1–12 (2010).
   PubMedGoogle Scholar
• Bossy-Wetzel E, Petrilli A, Knott AB. Mutant huntingtin and mitochondrial dysfunction. Trends Neurosci. 31(12), 609–616 (2008).
   PubMed Web of Science ®Google Scholar
• Rosenstock TR, Duarte AI, Rego AC. Mitochondrial-associated metabolic changes and neurodegeneration in Huntington’s disease – from clinical features to the bench. Curr. Drug Targets 11(10), 1218–1236 (2010).
   PubMedGoogle Scholar
• Lutha SS, Cicchetti D. The construct of resilience: implications for interventions and social policies. Dev. Psychopathol. 12(4), 857–885 (2000).
   PubMed Web of Science ®Google Scholar
• Feder A, Nestler EJ, Charney DS. Psychobiology and molecular genetics of resilience. Nat. Rev. Neurosci. 10(6), 446–457 (2009).
   PubMed Web of Science ®Google Scholar
• Cicchetti D, Rogosch FA. Adaptive coping under conditions of extreme stress: multilevel influences on the determinants of resilience in maltreated children. New Dir. Child Adolesc. Dev. 2009(124), 47–59 (2009).
   PubMedGoogle Scholar
• Rutter M, Moffitt TE, Caspi A. Gene–environment interplay and psychopathology: multiple varieties but real effects. J. Child Psychol. Psychiatr. 47(3–4), 226–261 (2006).
   PubMed Web of Science ®Google Scholar
• Caspi A, Sugden K, Moffitt TE et al. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301(5631), 386–389 (2003).
   PubMed Web of Science ®Google Scholar
• Suomi SJ. Risk, resilience, and gene–environment interplay in primates. J. Can. Acad. Child Adolesc. Psychiatr. 20(4), 289–297 (2011).
   PubMedGoogle Scholar
• Benedetti F, Poletti S, Radaelli D et al. Temporal lobe grey matter volume in schizophrenia is associated with a genetic polymorphism influencing glycogen synthase kinase 3-β activity. Genes Brain Behav. 9(4), 365–371 (2010).
   PubMedGoogle Scholar
• Schmidt MV, Trümbach D, Weber P et al. Individual stress vulnerability is predicted by short-term memory and AMPA receptor subunit ratio in the hippocampus. J. Neurosci. 30(50), 16949–16958 (2010).
   PubMed Web of Science ®Google Scholar
• Liberzon I, Knox D. Expanding our understanding of neurobiological mechanisms of resilience by using animal models. Neuropsychopharmacology 37(2), 317–318 (2012).
   PubMedGoogle Scholar
• Rasetti R, Weinberger DR. Intermediate phenotypes in psychiatric disorders. Curr. Opin. Genet. Dev. 21(3), 340–348 (2011).
   PubMed Web of Science ®Google Scholar
• Robison AJ, Nestler EJ. Transcriptional and epigenetic mechanisms of addiction. Nat. Rev. Neurosci. 12(11), 623–637 (2011).
   PubMed Web of Science ®Google Scholar
• Gottesman II, Gould TD. The endophenotype concept in psychiatry: etymology and strategic intentions. Am. J. Psychiatr. 160(4), 636–645 (2003).
   PubMed Web of Science ®Google Scholar
• Gershon ES, Alliey-Rodriguez N, Liu C. After GWAS: searching for genetic risk for schizophrenia and bipolar disorder. Am. J. Psychiatr. 168(3), 253–256 (2011).
   PubMed Web of Science ®Google Scholar
• Karayiorgou M, Simon TJ, Gogos JA. 22q11.2 microdeletions: linking DNA structural variation to brain dysfunction and schizophrenia. Nat. Rev. Neurosci. 11(6), 402–416 (2010).
   PubMed Web of Science ®Google Scholar
• Harrison PJ, Weinberger DR. Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol. Psychiatr. 10(1), 40–68; image 5 (2005).
   PubMed Web of Science ®Google Scholar
• Carter CJ. Schizophrenia susceptibility genes converge on interlinked pathways related to glutamatergic transmission and long-term potentiation, oxidative stress and oligodendrocyte viability. Schizophr. Res. 86(1–3), 1–14 (2006).
   PubMed Web of Science ®Google Scholar
• Lee FH, Fadel MP, Preston-Maher K et al. Disc1 point mutations in mice affect development of the cerebral cortex. J. Neurosci. 31(9), 3197–3206 (2011).
   PubMedGoogle Scholar
• Sigurdsson T, Stark KL, Karayiorgou M, Gogos JA, Gordon JA. Impaired hippocampal-prefrontal synchrony in a genetic mouse model of schizophrenia. Nature 464(7289), 763–767 (2010).
   PubMed Web of Science ®Google Scholar
• Kato T, Kasai A, Mizuno M et al. Phenotypic characterization of transgenic mice overexpressing neuregulin-1. PLoS ONE 5(12), e14185 (2010).
   Google Scholar
• Nestler EJ, Hyman SE. Animal models of neuropsychiatric disorders. Nat. Neurosci. 13(10), 1161–1169 (2010).
   PubMed Web of Science ®Google Scholar
• Schwab SG, Wildenauer DB. Update on key previously proposed candidate genes for schizophrenia. Curr. Opin. Psychiatr. 22(2), 147–153 (2009).
   PubMed Web of Science ®Google Scholar
• Petronis A, Gottesman II, Kan P et al. Monozygotic twins exhibit numerous epigenetic differences: clues to twin discordance? Schizophr. Bull. 29(1), 169–178 (2003).
   PubMed Web of Science ®Google Scholar
• Honea R, Crow TJ, Passingham D, Mackay CE. Regional deficits in brain volume in schizophrenia: a meta-analysis of voxel-based morphometry studies. Am. J. Psychiatr. 162(12), 2233–2245 (2005).
   PubMed Web of Science ®Google Scholar
• Meyer-Lindenberg A. Neuroimaging and the question of neurodegeneration in schizophrenia. Prog. Neurobiol. 95(4), 514–516 (2011).
   PubMedGoogle Scholar
• Lewis DA, Hashimoto T. Deciphering the disease process of schizophrenia: the contribution of cortical GABA neurons. Int. Rev. Neurobiol. 78, 109–131 (2007).
   PubMed Web of Science ®Google Scholar
• Jaaro-Peled H, Ayhan Y, Pletnikov MV, Sawa A. Review of pathological hallmarks of schizophrenia: comparison of genetic models with patients and nongenetic models. Schizophr. Bull. 36(2), 301–313 (2010).
   PubMedGoogle Scholar
• Volk DW, Lewis DA. Prefrontal cortical circuits in schizophrenia. Curr. Top. Behav. Neurosci. 4, 485–508 (2010).
   PubMedGoogle Scholar
• Brown AS, Patterson PH. The Origins of Schizophrenia. Columbia University Press, NY, USA (2012).
   Google Scholar
• Piontkewitz Y, Assaf Y, Weiner I. Clozapine administration in adolescence prevents postpubertal emergence of brain structural pathology in an animal model of schizophrenia. Biol. Psychiatr. 66(11), 1038–1046 (2009).
   PubMed Web of Science ®Google Scholar
• Piontkewitz Y, Arad M, Weiner I. Abnormal trajectories of neurodevelopment and behavior following in utero insult in the rat. Biol. Psychiatr. 70(9), 842–851 (2011).
   PubMedGoogle Scholar
• Lodge DJ, Grace AA. Hippocampal dysfunction and disruption of dopamine system regulation in an animal model of schizophrenia. Neurotox. Res. 14(2–3), 97–104 (2008).
   PubMed Web of Science ®Google Scholar
• Walker EF, Diforio D. Schizophrenia: a neural diathesis-stress model. Psychol. Rev. 104(4), 667–685 (1997).
   PubMed Web of Science ®Google Scholar
• Jones SR, Fernyhough C. A new look at the neural diathesis–stress model of schizophrenia: the primacy of social-evaluative and uncontrollable situations. Schizophr. Bull. 33(5), 1171–1177 (2007).
   PubMed Web of Science ®Google Scholar
• van Os J, Kenis G, Rutten BP. The environment and schizophrenia. Nature 468(7321), 203–212 (2010).
   PubMed Web of Science ®Google Scholar
• Potvin S, Stip E, Roy J. Schizophrenia and addiction: an evaluation of the self-medication hypothesis. L’Enceéphale 29(3), 193–203 (2003).
   PubMed Web of Science ®Google Scholar
• Bayer TA, Falkai P, Maier W. Genetic and non-genetic vulnerability factors in schizophrenia: the basis of the ‘two hit hypothesis’. J. Psychiatr. Res. 33(6), 543–548 (1999).
   PubMed Web of Science ®Google Scholar
• Lieberman JA, Bymaster FP, Meltzer HY et al. Antipsychotic drugs: comparison in animal models of efficacy, neurotransmitter regulation, and neuroprotection. Pharmacol. Rev. 60(3), 358–403 (2008).
   PubMed Web of Science ®Google Scholar
• Abi-Dargham A, van de Giessen E, Slifstein M, Kegeles LS, Laruelle M. Baseline and amphetamine-stimulated dopamine activity are related in drug-naïve schizophrenic subjects. Biol. Psychiatr. 65(12), 1091–1093 (2009).
   PubMed Web of Science ®Google Scholar
• Kellendonk C, Simpson EH, Polan HJ et al. Transient and selective overexpression of dopamine D2 receptors in the striatum causes persistent abnormalities in prefrontal cortex functioning. Neuron 49(4), 603–615 (2006).
   PubMed Web of Science ®Google Scholar
• Simpson EH, Kellendonk C, Kandel E. A possible role for the striatum in the pathogenesis of the cognitive symptoms of schizophrenia. Neuron 65(5), 585–596 (2010).
   PubMed Web of Science ®Google Scholar
• Guillin O, Abi-Dargham A, Laruelle M. Neurobiology of dopamine in schizophrenia. Int. Rev. Neurobiol. 78, 1–39 (2007).
   PubMed Web of Science ®Google Scholar
• Moghaddam B, Javitt D. From revolution to evolution: the glutamate hypothesis of schizophrenia and its implication for treatment. Neuropsychopharmacology 37(1), 4–15 (2012).
   PubMed Web of Science ®Google Scholar
• Shim G, Kang DH, Chung YS, Yoo SY, Shin NY, Kwon JS. Social functioning deficits in young people at risk for schizophrenia. Aust. NZ J. Psychiatr. 42(8), 678–685 (2008).
   PubMed Web of Science ®Google Scholar
• Patil ST, Zhang L, Martenyi F et al. Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial. Nat. Med. 13(9), 1102–1107 (2007).
   PubMed Web of Science ®Google Scholar
• Moore H. The role of rodent models in the discovery of new treatments for schizophrenia: updating our strategy. Schizophr. Bull. 36(6), 1066–1072 (2010).
   PubMed Web of Science ®Google Scholar
• Geyer MA. Developing translational animal models for symptoms of schizophrenia or bipolar mania. Neurotox. Res. 14(1), 71–78 (2008).
   PubMed Web of Science ®Google Scholar
• Papaleo F, Lipska BK, Weinberger DR. Mouse models of genetic effects on cognition: relevance to schizophrenia. Neuropharmacology 62(3), 1204–1220 (2012).
   PubMedGoogle Scholar
• Dow LE, Lowe SW. Life in the fast lane: mammalian disease models in the genomics era. Cell 148(6), 1099–1109 (2012).
   PubMedGoogle Scholar
• Arguello PA, Markx S, Gogos JA, Karayiorgou M. Development of animal models for schizophrenia. Dis. Model. Mech. 3(1–2), 22–26 (2010).
   PubMed Web of Science ®Google Scholar
• Bitanihirwe BK, Lim MP, Kelley JF, Kaneko T, Woo TU. Glutamatergic deficits and parvalbumin-containing inhibitory neurons in the prefrontal cortex in schizophrenia. BMC Psychiatr. 9, 71 (2009).
   PubMed Web of Science ®Google Scholar
• Mohn AR, Gainetdinov RR, Caron MG, Koller BH. Mice with reduced NMDA receptor expression display behaviors related to schizophrenia. Cell 98(4), 427–436 (1999).
   PubMed Web of Science ®Google Scholar
• Belforte JE, Zsiros V, Sklar ER et al. Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes. Nat. Neurosci. 13(1), 76–83 (2010).
   PubMed Web of Science ®Google Scholar
• Enna SJ, Williams M. Challenges in the search for drugs to treat central nervous system disorders. J. Pharmacol. Exp. Ther. 329(2), 404–411 (2009).
   PubMed Web of Science ®Google Scholar
• Skarnes WC, Rosen B, West AP et al. A conditional knockout resource for the genome-wide study of mouse gene function. Nature 474(7351), 337–342 (2011).
   PubMed Web of Science ®Google Scholar
• Dow LE, Premsrirut PK, Zuber J et al. A pipeline for the generation of shRNA transgenic mice. Nat. Protoc. 7(2), 374–393 (2012).
   PubMed Web of Science ®Google Scholar
• Arguello PA, Gogos JA. Modeling madness in mice: one piece at a time. Neuron 52(1), 179–196 (2006).
   PubMed Web of Science ®Google Scholar
• Kegeles LS, Abi-Dargham A, Frankle WG et al. Increased synaptic dopamine function in associative regions of the striatum in schizophrenia. Arch. Gen. Psychiatr. 67(3), 231–239 (2010).
   PubMed Web of Science ®Google Scholar
• Nordström AL, Farde L, Wiesel FA et al. Central D2-dopamine receptor occupancy in relation to antipsychotic drug effects: a double-blind PET study of schizophrenic patients. Biol. Psychiatr. 33(4), 227–235 (1993).
   PubMed Web of Science ®Google Scholar
• Weiner I, Arad M. Using the pharmacology of latent inhibition to model domains of pathology in schizophrenia and their treatment. Behav. Brain Res. 204(2), 369–386 (2009).
   PubMedGoogle Scholar
• Schmidt-Hansen M, Le Pelley M. The positive symptoms of acute schizophrenia and latent inhibition in humans and animals: underpinned by the same process(es)? Cogn. Neuropsychiatr. doi:10.1080/13546805.2012.667202 (2012) (Epub ahead of print).
   PubMedGoogle Scholar
• Gaisler-Salomon I, Weiner I. Systemic administration of MK-801 produces an abnormally persistent latent inhibition which is reversed by clozapine but not haloperidol. Psychopharmacology 166(4), 333–342 (2003).
   PubMedGoogle Scholar
• Gaisler-Salomon I, Diamant L, Rubin C, Weiner I. Abnormally persistent latent inhibition induced by MK801 is reversed by risperidone and by positive modulators of NMDA receptor function: differential efficacy depending on the stage of the task at which they are administered. Psychopharmacology 196(2), 255–267 (2008).
   PubMedGoogle Scholar
• Lipina T, Labrie V, Weiner I, Roder J. Modulators of the glycine site on NMDA receptors, d-serine and ALX 5407, display similar beneficial effects to clozapine in mouse models of schizophrenia. Psychopharmacology 179(1), 54–67 (2005).
   PubMed Web of Science ®Google Scholar
• Labrie V, Lipina T, Roder JC. Mice with reduced NMDA receptor glycine affinity model some of the negative and cognitive symptoms of schizophrenia. Psychopharmacology 200(2), 217–230 (2008).
   PubMed Web of Science ®Google Scholar
• Swerdlow NR, Geyer MA, Braff DL. Neural circuit regulation of prepulse inhibition of startle in the rat: current knowledge and future challenges. Psychopharmacology 156(2–3), 194–215 (2001).
   PubMed Web of Science ®Google Scholar
• Ralph RJ, Varty GB, Kelly MA et al. The dopamine D2, but not D3 or D4, receptor subtype is essential for the disruption of prepulse inhibition produced by amphetamine in mice. J. Neurosci. 19(11), 4627–4633 (1999).
   PubMedGoogle Scholar
• Geyer MA, Krebs-Thomson K, Braff DL, Swerdlow NR. Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review. Psychopharmacology 156(2–3), 117–154 (2001).
   PubMed Web of Science ®Google Scholar
• Brody SA, Conquet F, Geyer MA. Effect of antipsychotic treatment on the prepulse inhibition deficit of mGluR5 knockout mice. Psychopharmacology 172(2), 187–195 (2004).
   PubMed Web of Science ®Google Scholar
• Ouagazzal AM, Jenck F, Moreau JL. Drug-induced potentiation of prepulse inhibition of acoustic startle reflex in mice: a model for detecting antipsychotic activity? Psychopharmacology 156(2–3), 273–283 (2001).
   PubMedGoogle Scholar
• Hagan JJ, Jones DN. Predicting drug efficacy for cognitive deficits in schizophrenia. Schizophr. Bull. 31(4), 830–853 (2005).
   PubMed Web of Science ®Google Scholar
• Keefe RS, Eesley CE, Poe MP. Defining a cognitive function decrement in schizophrenia. Biol. Psychiatr. 57(6), 688–691 (2005).
   PubMed Web of Science ®Google Scholar
• Keefe RS, Sweeney JA, Gu H et al. Effects of olanzapine, quetiapine, and risperidone on neurocognitive function in early psychosis: a randomized, double-blind 52-week comparison. Am. J. Psychiatr. 164(7), 1061–1071 (2007).
   PubMed Web of Science ®Google Scholar
• Black MD, Stevens RJ, Rogacki N et al. AVE1625, a cannabinoid CB1 receptor antagonist, as a co-treatment with antipsychotics for schizophrenia: improvement in cognitive function and reduction of antipsychotic-side effects in rodents. Psychopharmacology 215(1), 149–163 (2011).
   PubMedGoogle Scholar
• Moore TL, Killiany RJ, Herndon JG, Rosene DL, Moss MB. A non-human primate test of abstraction and set shifting: an automated adaptation of the Wisconsin Card Sorting Test. J. Neurosci. Methods 146(2), 165–173 (2005).
   PubMed Web of Science ®Google Scholar
• Dias R, Robbins TW, Roberts AC. Primate analogue of the Wisconsin Card Sorting Test: effects of excitotoxic lesions of the prefrontal cortex in the marmoset. Behav. Neurosci. 110(5), 872–886 (1996).
   PubMed Web of Science ®Google Scholar
• Birrell JM, Brown VJ. Medial frontal cortex mediates perceptual attentional set shifting in the rat. J. Neurosci. 20(11), 4320–4324 (2000).
   PubMed Web of Science ®Google Scholar
• Dias R, Aggleton JP. Effects of selective excitotoxic prefrontal lesions on acquisition of nonmatching- and matching-to-place in the T-maze in the rat: differential involvement of the prelimbic–infralimbic and anterior cingulate cortices in providing behavioural flexibility. Eur. J. Neurosci. 12(12), 4457–4466 (2000).
   PubMedGoogle Scholar
• Arguello PA, Gogos JA. Cognition in mouse models of schizophrenia susceptibility genes. Schizophr. Bull. 36(2), 289–300 (2010).
   PubMedGoogle Scholar
• Coyle JT, Tsai G. The NMDA receptor glycine modulatory site: a therapeutic target for improving cognition and reducing negative symptoms in schizophrenia. Psychopharmacology 174(1), 32–38 (2004).
   PubMedGoogle Scholar
• Martina M, Gorfinkel Y, Halman S et al. 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(Pt 2), 489–500 (2004).
   PubMed Web of Science ®Google Scholar
• Tsai G, Ralph-Williams RJ, Martina M et al. Gene knockout of glycine transporter 1: characterization of the behavioral phenotype. Proc. Natl Acad. Sci. USA 101(22), 8485–8490 (2004).
   PubMed Web of Science ®Google Scholar
• Singer P, Boison D, Möhler H, Feldon J, Yee BK. Enhanced recognition memory following glycine transporter 1 deletion in forebrain neurons. Behav. Neurosci. 121(5), 815–825 (2007).
   PubMedGoogle Scholar
• Yee BK, Balic E, Singer P et al. Disruption of glycine transporter 1 restricted to forebrain neurons is associated with a procognitive and antipsychotic phenotypic profile. J. Neurosci. 26(12), 3169–3181 (2006).
   PubMed Web of Science ®Google Scholar
• Singer P, Boison D, Möhler H, Feldon J, Yee BK. Modulation of sensorimotor gating in prepulse inhibition by conditional brain glycine transporter 1 deletion in mice. Eur. Neuropsychopharmacol. 21(5), 401–413 (2011).
   PubMedGoogle Scholar
• Kinney GG, Sur C, Burno M et al. The glycine transporter type 1 inhibitor N-[3-(4’-fluorophenyl)-3-(4’-phenylphenoxy)propyl]sarcosine potentiates NMDA receptor-mediated responses in vivo and produces an antipsychotic profile in rodent behavior. J. Neurosci. 23(20), 7586–7591 (2003).
   PubMed Web of Science ®Google Scholar
• Möhler H, Boison D, Singer P, Feldon J, Pauly-Evers M, Yee BK. Glycine transporter 1 as a potential therapeutic target for schizophrenia-related symptoms: evidence from genetically modified mouse models and pharmacological inhibition. Biochem. Pharmacol. 81(9), 1065–1077 (2011).
   PubMed Web of Science ®Google Scholar
• Bergeron R, Meyer TM, Coyle JT, Greene RW. Modulation of N-methyl-d-aspartate receptor function by glycine transport. Proc. Natl Acad. Sci. USA 95(26), 15730–15734 (1998).
   PubMed Web of Science ®Google Scholar
• Atkinson BN, Bell SC, De Vivo M et al. ALX 5407: a potent, selective inhibitor of the hGlyT1 glycine transporter. Mol. Pharmacol. 60(6), 1414–1420 (2001).
   PubMed Web of Science ®Google Scholar
• Brown A, Carlyle I, Clark J et al. Discovery and SAR of org 24598 – a selective glycine uptake inhibitor. Bioorg. Med. Chem. Lett. 11(15), 2007–2009 (2001).
   PubMed Web of Science ®Google Scholar
• Harsing LG Jr, Gacsalyi I, Szabo G et al. The glycine transporter-1 inhibitors NFPS and Org 24461: a pharmacological study. Pharmacol. Biochem. Behav. 74(4), 811–825 (2003).
   PubMedGoogle Scholar
• Depoortère R, Dargazanli G, Estenne-Bouhtou G et al. Neurochemical, electrophysiological and pharmacological profiles of the selective inhibitor of the glycine transporter-1 SSR504734, a potential new type of antipsychotic. Neuropsychopharmacology 30(11), 1963–1985 (2005).
   PubMed Web of Science ®Google Scholar
• Pinard E, Alanine A, Alberati D et al. Selective GlyT1 inhibitors: discovery of [4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl][5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methylethoxy)phenyl]methanone (RG1678), a promising novel medicine to treat schizophrenia. J. Med. Chem. 53(12), 4603–4614 (2010).
   PubMed Web of Science ®Google Scholar
• Sasaki M, Konno R, Nishio M, Niwa A, Yasumura Y, Enami J. A single-base-pair substitution abolishes d-amino-acid oxidase activity in the mouse. Biochim. Biophys. Acta 1139(4), 315–318 (1992).
   PubMedGoogle Scholar
• Hashimoto A, Konno R, Yano H et al. Mice lacking d-amino acid oxidase activity exhibit marked reduction of methamphetamine-induced stereotypy. Eur. J. Pharmacol. 586(1–3), 221–225 (2008).
   PubMedGoogle Scholar
• Labrie V, Wong AH, Roder JC. Contributions of the d-serine pathway to schizophrenia. Neuropharmacology 62(3), 1484–1503 (2012).
   PubMedGoogle Scholar
• Panizzutti R, Rausch M, Zurbrügg S, Baumann D, Beckmann N, Rudin M. The pharmacological stimulation of NMDA receptors via co-agonist site: an fMRI study in the rat brain. Neurosci. Lett. 380(1–2), 111–115 (2005).
   PubMedGoogle Scholar
• Konno R, Yasumura Y. Mouse mutant deficient in d-amino acid oxidase activity. Genetics 103(2), 277–285 (1983).
   PubMed Web of Science ®Google Scholar
• Wake K, Yamazaki H, Hanzawa S et al. Exaggerated responses to chronic nociceptive stimuli and enhancement of N-methyl-d-aspartate receptor-mediated synaptic transmission in mutant mice lacking d-amino-acid oxidase. Neurosci. Lett. 297(1), 25–28 (2001).
   PubMedGoogle Scholar
• Labrie V, Wang W, Barger SW, Baker GB, Roder JC. Genetic loss of d-amino acid oxidase activity reverses schizophrenia-like phenotypes in mice. Genes Brain Behav. 9(1), 11–25 (2010).
   PubMedGoogle Scholar
• Hashimoto A, Yoshikawa M, Niwa A, Konno R. Mice lacking d-amino acid oxidase activity display marked attenuation of stereotypy and ataxia induced by MK-801. Brain Res. 1033(2), 210–215 (2005).
   PubMedGoogle Scholar
• Zhang M, Ballard ME, Basso AM et al. Behavioral characterization of a mutant mouse strain lacking d-amino acid oxidase activity. Behav. Brain Res. 217(1), 81–87 (2011).
   PubMedGoogle Scholar
• Almond SL, Fradley RL, Armstrong EJ et al. Behavioral and biochemical characterization of a mutant mouse strain lacking D-amino acid oxidase activity and its implications for schizophrenia. Mol. Cell. Neurosci. 32(4), 324–334 (2006).
   PubMedGoogle Scholar
• Labrie V, Duffy S, Wang W, Barger SW, Baker GB, Roder JC. Genetic inactivation of d-amino acid oxidase enhances extinction and reversal learning in mice. Learn. Mem. 16(1), 28–37 (2009).
   PubMed Web of Science ®Google Scholar
• Maekawa M, Watanabe M, Yamaguchi S, Konno R, Hori Y. Spatial learning and long-term potentiation of mutant mice lacking d-amino-acid oxidase. Neurosci. Res. 53(1), 34–38 (2005).
   PubMedGoogle Scholar
• Tsai G, Yang P, Chung LC, Lange N, Coyle JT. d-serine added to antipsychotics for the treatment of schizophrenia. Biol. Psychiatr. 44(11), 1081–1089 (1998).
   PubMed Web of Science ®Google Scholar
• Heresco-Levy U, Javitt DC, Ebstein R et al. d-serine efficacy as add-on pharmacotherapy to risperidone and olanzapine for treatment-refractory schizophrenia. Biol. Psychiatr. 57(6), 577–585 (2005).
   PubMed Web of Science ®Google Scholar
• Gottlieb JD, Cather C, Shanahan M, Creedon T, Macklin EA, Goff DC. d-cycloserine facilitation of cognitive behavioral therapy for delusions in schizophrenia. Schizophr. Res. 131(1–3), 69–74 (2011).
   PubMed Web of Science ®Google Scholar
• Buchanan RW, Javitt DC, Marder SR et al. The Cognitive and Negative Symptoms in Schizophrenia Trial (CONSIST): the efficacy of glutamatergic agents for negative symptoms and cognitive impairments. Am. J. Psychiatr. 164(10), 1593–1602 (2007).
   PubMed Web of Science ®Google Scholar
• Chung SP, Sogabe K, Park HK et al. Potential cytotoxic effect of hydroxypyruvate produced from d-serine by astroglial d-amino acid oxidase. J. Biochem. 148(6), 743–753 (2010).
   PubMedGoogle Scholar
• Park HK, Shishido Y, Ichise-Shishido S et al. Potential role for astroglial d-amino acid oxidase in extracellular d-serine metabolism and cytotoxicity. J. Biochem. 139(2), 295–304 (2006).
   PubMedGoogle Scholar
• Brandish PE, Chiu CS, Schneeweis J et al. A cell-based ultra-high-throughput screening assay for identifying inhibitors of d-amino acid oxidase. J. Biomol. Screen. 11(5), 481–487 (2006).
   PubMedGoogle Scholar
• Verrall L, Burnet PW, Betts JF, Harrison PJ. The neurobiology of d-amino acid oxidase and its involvement in schizophrenia. Mol. Psychiatr. 15(2), 122–137 (2010).
   PubMed Web of Science ®Google Scholar
• Yagi K, Nagatsu T, Ozawa T. Inhibitory action of chlorpromazine on the oxidation of d-amino-acid in the diencephalon part of the brain. Nature 177(4515), 891–892 (1956).
   PubMedGoogle Scholar
• Iwana S, Kawazoe T, Park HK et al. Chlorpromazine oligomer is a potentially active substance that inhibits human d-amino acid oxidase, product of a susceptibility gene for schizophrenia. J. Enzyme Inhib. Med. Chem. 23(6), 901–911 (2008).
   PubMed Web of Science ®Google Scholar
• Moghaddam B, Adams B, Verma A, Daly D. 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(8), 2921–2927 (1997).
   PubMed Web of Science ®Google Scholar
• Razoux F, Garcia R, Léna I. Ketamine, at a dose that disrupts motor behavior and latent inhibition, enhances prefrontal cortex synaptic efficacy and glutamate release in the nucleus accumbens. Neuropsychopharmacology 32(3), 719–727 (2007).
   PubMed Web of Science ®Google Scholar
• Takahata R, Moghaddam B. Activation of glutamate neurotransmission in the prefrontal cortex sustains the motoric and dopaminergic effects of phencyclidine. Neuropsychopharmacology 28(6), 1117–1124 (2003).
   PubMedGoogle Scholar
• Moghaddam B. Bringing order to the glutamate chaos in schizophrenia. Neuron 40(5), 881–884 (2003).
   PubMed Web of Science ®Google Scholar
• Karlsson RM, Tanaka K, Heilig M, Holmes A. Loss of glial glutamate and aspartate transporter (excitatory amino acid transporter 1) causes locomotor hyperactivity and exaggerated responses to psychotomimetics: rescue by haloperidol and metabotropic glutamate 2/3 agonist. Biol. Psychiatr. 64(9), 810–814 (2008).
   PubMedGoogle Scholar
• Yizhar O, Fenno LE, Prigge M et al. Neocortical excitation/inhibition balance in information processing and social dysfunction. Nature 477(7363), 171–178 (2011).
   PubMed Web of Science ®Google Scholar
• Théberge J, Bartha R, Drost DJ et al. Glutamate and glutamine measured with 4.0 T proton MRS in never-treated patients with schizophrenia and healthy volunteers. Am. J. Psychiatr. 159(11), 1944–1946 (2002).
   PubMed Web of Science ®Google Scholar
• Tibbo P, Hanstock C, Valiakalayil A, Allen P. 3-T proton MRS investigation of glutamate and glutamine in adolescents at high genetic risk for schizophrenia. Am. J. Psychiatr. 161(6), 1116–1118 (2004).
   PubMedGoogle Scholar
• Zoccali R, Muscatello MR, Bruno A et al. The effect of lamotrigine augmentation of clozapine in a sample of treatment-resistant schizophrenic patients: a double-blind, placebo-controlled study. Schizophr. Res. 93(1–3), 109–116 (2007).
   PubMed Web of Science ®Google Scholar
• Gaisler-Salomon I, Miller GM, Chuhma N et al. Glutaminase-deficient mice display hippocampal hypoactivity, insensitivity to pro-psychotic drugs and potentiated latent inhibition: relevance to schizophrenia. Neuropsychopharmacology 34(10), 2305–2322 (2009).
   PubMed Web of Science ®Google Scholar
• Masson J, Darmon M, Conjard A et al. Mice lacking brain/kidney phosphate-activated glutaminase have impaired glutamatergic synaptic transmission, altered breathing, disorganized goal-directed behavior and die shortly after birth. J. Neurosci. 26(17), 4660–4671 (2006).
   PubMed Web of Science ®Google Scholar
• Cavazzuti M, Porro CA, Biral GP, Benassi C, Barbieri GC. Ketamine effects on local cerebral blood flow and metabolism in the rat. J. Cereb. Blood Flow Metab. 7(6), 806–811 (1987).
   PubMed Web of Science ®Google Scholar
• Gaisler-Salomon I, Wang Y, Chuhma N et al. Synaptic underpinnings of altered hippocampal function in glutaminase-deficient mice during maturation. Hippocampus 22(5), 1027–1039 (2012).
   PubMed Web of Science ®Google Scholar
• Schobel SA, Lewandowski NM, Corcoran CM et al. Differential targeting of the CA1 subfield of the hippocampal formation by schizophrenia and related psychotic disorders. Arch. Gen. Psychiatr. 66(9), 938–946 (2009).
   PubMed Web of Science ®Google Scholar
• Flores C, Manitt C, Rodaros D et al. Netrin receptor deficient mice exhibit functional reorganization of dopaminergic systems and do not sensitize to amphetamine. Mol. Psychiatr. 10(6), 606–612 (2005).
   PubMedGoogle Scholar
• Manitt C, Mimee A, Eng C et al. The netrin receptor DCC is required in the pubertal organization of mesocortical dopamine circuitry. J. Neurosci. 31(23), 8381–8394 (2011).
   PubMedGoogle Scholar
• Yetnikoff L, Eng C, Benning S, Flores C. Netrin-1 receptor in the ventral tegmental area is required for sensitization to amphetamine. Eur. J. Neurosci. 31(7), 1292–1302 (2010).
   PubMedGoogle Scholar
• Srour M, Rivière JB, Pham JM et al. Mutations in DCC cause congenital mirror movements. Science 328(5978), 592 (2010).
   PubMedGoogle Scholar
• Bibb JA. Decoding dopamine signaling. Cell 122(2), 153–155 (2005).
   PubMedGoogle Scholar
• Beaulieu JM, Sotnikova TD, Yao WD et al. Lithium antagonizes dopamine-dependent behaviors mediated by an AKT/glycogen synthase kinase 3 signaling cascade. Proc. Natl Acad. Sci. USA 101(14), 5099–5104 (2004).
   PubMed Web of Science ®Google Scholar
• Beaulieu JM, Sotnikova TD, Marion S, Lefkowitz RJ, Gainetdinov RR, Caron MG. An Akt/beta-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior. Cell 122(2), 261–273 (2005).
   PubMed Web of Science ®Google Scholar
• Svenningsson P, Tzavara ET, Carruthers R et al. Diverse psychotomimetics act through a common signaling pathway. Science 302(5649), 1412–1415 (2003).
   PubMed Web of Science ®Google Scholar
• Allen JA, Yost JM, Setola V et al. Discovery of β-arrestin-biased dopamine D2 ligands for probing signal transduction pathways essential for antipsychotic efficacy. Proc. Natl Acad. Sci. USA 108(45), 18488–18493 (2011).
   PubMed Web of Science ®Google Scholar
• Mallon AM, Blake A, Hancock JM. EuroPhenome and EMPReSS: online mouse phenotyping resource. Nucleic Acids Res. 36(Database issue), D715–D718 (2008).
   Google Scholar
• Dempster EL, Pidsley R, Schalkwyk LC et al. Disease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder. Hum. Mol. Genet. 20(24), 4786–4796 (2011).
   PubMed Web of Science ®Google Scholar
• Ramboz S, Oosting R, Amara DA et al. Serotonin receptor 1A knockout: an animal model of anxiety-related disorder. Proc. Natl Acad. Sci. USA 95(24), 14476–14481 (1998).
   PubMed Web of Science ®Google Scholar
• Ansorge MS, Zhou M, Lira A, Hen R, Gingrich JA. Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice. Science 306(5697), 879–881 (2004).
   PubMed Web of Science ®Google Scholar
• Giros B, Jaber M, Jones SR, Wightman RM, Caron MG. Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature 379(6566), 606–612 (1996).
   PubMed Web of Science ®Google Scholar
• Gellman C, Mingote S, Wang Y, Gaisler-Salomon I, Rayport S. Genetic pharmacotherapy. In: Drug Discovery and Development – Present and Future. Kapetanovic I (Ed.). InTech, Rijeka, Croatia, 125–150 (2011).
   Google Scholar
• Abbott A. Novartis to shut brain research facility. Nature 480(7376), 161–162 (2011).
   PubMed Web of Science ®Google Scholar
• Chiamulera C, Epping-Jordan MP, Zocchi A et al. Reinforcing and locomotor stimulant effects of cocaine are absent in mGluR5 null mutant mice. Nat. Neurosci. 4(9), 873–874 (2001).
   PubMed Web of Science ®Google Scholar
• Heurteaux C, Lucas G, Guy N et al. Deletion of the background potassium channel TREK-1 results in a depression-resistant phenotype. Nat. Neurosci. 9(9), 1134–1141 (2006).
   PubMed Web of Science ®Google Scholar
• Zhang Y, Kurup P, Xu J et al. Genetic reduction of striatal-enriched tyrosine phosphatase (STEP) reverses cognitive and cellular deficits in an Alzheimer’s disease mouse model. Proc. Natl Acad. Sci. USA 107(44), 19014–19019 (2010).
   PubMedGoogle Scholar
• Oliveira TG, Chan RB, Tian H et al. Phospholipase d2 ablation ameliorates Alzheimer’s disease-linked synaptic dysfunction and cognitive deficits. J. Neurosci. 30(49), 16419–16428 (2010).
   PubMed Web of Science ®Google Scholar
• Tang YP, Shimizu E, Dube GR et al. Genetic enhancement of learning and memory in mice. Nature 401(6748), 63–69 (1999).
   PubMed Web of Science ®Google Scholar
• Cao X, Cui Z, Feng R et al. Maintenance of superior learning and memory function in NR2B transgenic mice during ageing. Eur. J. Neurosci. 25(6), 1815–1822 (2007).
   PubMedGoogle Scholar
• Gaisler-Salomon I, Wang Y, Mckinney S et al. Adult-onset glutamate receptor expression deficits in the hippocampus of glutaminase-deficient mice. Biol. Psychiatr. 67, S71 (2010).
   PubMedGoogle Scholar