Behavioral Animal Models of Antipsychotic Drug Actions

  • Daria Peleg-Raibstein
  • Joram FeldonEmail author
  • Urs Meyer
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 212)


Basic research in animals represents a fruitful approach to study the neurobiological basis of brain and behavioral disturbances relevant to neuropsychiatric disease and to establish and evaluate novel pharmacological therapies for their treatment. In the context of schizophrenia, there are models employing specific experimental manipulations developed according to specific pathophysiological or etiological hypotheses. The use of selective lesions in adult animals and the acute administration of psychotomimetic agents are indispensable tools in the elucidation of the contribution of specific brain regions or neurotransmitters to the genesis of a specific symptom or collection of symptoms and enjoy some degrees of predictive validity. However, they may be inaccurate, if not inadequate, in capturing the etiological mechanisms or ontology of the disease needed for a complete understanding of the disease and may be limited in the discovery of novel compounds for the treatment of negative and cognitive symptoms of schizophrenia. Under the prevailing consensus of schizophrenia as a disease of neurodevelopmental origin, we have seen the establishment of neurodevelopmental animal models which aim to identify the etiological processes whereby the brain, following specific triggering events, develops into a “schizophrenia-like brain” over time. Many neurodevelopmental models such as the neonatal ventral hippocampus (vHPC) lesion, methylazoxymethanol (MAM), and prenatal immune activation models can mimic a broad spectrum of behavioral, cognitive, and pharmacological abnormalities directly implicated in schizophrenic disease. These models allow pharmacological screens against multiple and coexisting schizophrenia-related dysfunctions while incorporating the disease-relevant concept of abnormal brain development. The multiplicity of existing models is testimonial to the multifactorial nature of schizophrenia, and there are ample opportunities for their integration. Indeed, one ultimate goal must be to incorporate the successes of distinct models into one unitary account of the complex disorder of schizophrenia and to use such unitary approaches in the further development and evaluation of novel antipsychotic treatment strategies.


Animal model Antipsychotic drugs Cognition Negative symptoms Positive symptoms Psychosis Schizophrenia 


  1. Abazyan B, Nomura J, Kannan G, Ishizuka K, Tamashiro KL, Nucifora F, Pogorelov V, Ladenheim B, Yang C, Krasnova IN, Cadet JL, Pardo C, Mori S, Kamiya A, Vogel MW, Sawa A, Ross CA, Pletnikov MV (2010) Prenatal interaction of mutant DISC1 and immune activation produces adult psychopathology. Biol Psychiatry 68:1172–1181PubMedCrossRefGoogle Scholar
  2. Abekawa T, Ito K, Nakagawa S, Koyama T (2007) Prenatal exposure to an NMDA receptor antagonist, MK-801 reduces density of parvalbumin-immunoreactive GABAergic neurons in the medial prefrontal cortex and enhances phencyclidine-induced hyperlocomotion but not behavioral sensitization to methamphetamine in postpubertal rats. Psychopharmacology (Berl) 192:303–316CrossRefGoogle Scholar
  3. Abi-Dargham A, Laruelle M, Aghajanian GK, Charney D, Krystal J (1997) The role of serotonin in the pathophysiology and treatment of schizophrenia. J Neuropsychiatry Clin Neurosci 9:1–17PubMedGoogle Scholar
  4. Aguilar-Valles A, Flores C, Luheshi GN (2010) Prenatal inflammation-induced hypoferremia alters dopamine function in the adult offspring in rat: relevance for schizophrenia. PLoS One 5:e10967PubMedCrossRefGoogle Scholar
  5. Aguilar-Valles A, Luheshi GN (2011) Alterations in cognitive function and behavioral response to amphetamine induced by prenatal inflammation are dependent on the stage of pregnancy. Psychoneuroendocrinology 36:634–648PubMedCrossRefGoogle Scholar
  6. Al-Amin HA, Shannon Weickert C, Weinberger DR, Lipska BK (2001) Delayed onset of enhanced MK-801-induced motor hyperactivity after neonatal lesions of the rat ventral hippocampus. Biol Psychiatry 49:528–539PubMedCrossRefGoogle Scholar
  7. Amitai N, Markou A (2010) Disruption of performance in the five-choice serial reaction time task induced by administration of N-methyl-D-aspartate receptor antagonists: relevance to cognitive dysfunction in schizophrenia. Biol Psychiatry 68:5–16PubMedCrossRefGoogle Scholar
  8. Amitai N, Semenova S, Markou A (2007) Cognitive-disruptive effects of the psychotomimetic phencyclidine and attenuation by atypical antipsychotic medications in rats. Psychopharmacology (Berl) 193:521–537CrossRefGoogle Scholar
  9. Andersen JD, Pouzet B (2004) Spatial memory deficits induced by perinatal treatment of rats with PCP and reversal effect of D-serine. Neuropsychopharmacology 29:1080–1090PubMedCrossRefGoogle Scholar
  10. Arguello PA, Gogos JA (2006) Modeling madness in mice: one piece at a time. Neuron 52:179–196PubMedCrossRefGoogle Scholar
  11. Ayhan Y, Abazyan B, Nomura J, Kim R, Ladenheim B, Krasnova IN, Sawa A, Margolis RL, Cadet JL, Mori S, Vogel MW, Ross CA, Pletnikov MV (2011) Differential effects of prenatal and postnatal expressions of mutant human DISC1 on neurobehavioral phenotypes in transgenic mice: evidence for neurodevelopmental origin of major psychiatric disorders. Mol Psychiatry 16:293–306PubMedCrossRefGoogle Scholar
  12. Babovic D, O’Tuathaigh CM, O’Connor AM, O’Sullivan GJ, Tighe O, Croke DT, Karayiorgou M, Gogos JA, Cotter D, Waddington JL (2008) Phenotypic characterization of cognition and social behavior in mice with heterozygous versus homozygous deletion of catechol-O-methyltransferase. Neuroscience 155:1021–1029PubMedCrossRefGoogle Scholar
  13. Babovic D, O’Tuathaigh CM, O’Sullivan GJ, Clifford JJ, Tighe O, Croke DT, Karayiorgou M, Gogos JA, Cotter D, Waddington JL (2007) Exploratory and habituation phenotype of heterozygous and homozygous COMT knockout mice. Behav Brain Res 183:236–239PubMedCrossRefGoogle Scholar
  14. Baier PC, Blume A, Koch J, Marx A, Fritzer G, Aldenhoff JB, Schiffelholz T (2009) Early postnatal depletion of NMDA receptor development affects behaviour and NMDA receptor expression until later adulthood in rats–a possible model for schizophrenia. Behav Brain Res 205:96–101PubMedCrossRefGoogle Scholar
  15. Ballard TM, Pauly-Evers M, Higgins GA, Ouagazzal AM, Mutel V, Borroni E, Kemp JA, Bluethmann H, Kew JN (2002) Severe impairment of NMDA receptor function in mice carrying targeted point mutations in the glycine binding site results in drug-resistant nonhabituating hyperactivity. J Neurosci 22:6713–6723PubMedGoogle Scholar
  16. Barak S (2009) Modeling cholinergic aspects of schizophrenia: focus on the antimuscarinic syndrome. Behav Brain Res 204:335–351PubMedCrossRefGoogle Scholar
  17. Barak S, Weiner I (2011) Putative cognitive enhancers in preclinical models related to schizophrenia: the search for an elusive target. Pharmacol Biochem Behav 99:164–189PubMedCrossRefGoogle Scholar
  18. Barch DM, Braver TS, Carter CS, Poldrack RA, Robbins TW (2009a) CNTRICS final task selection: executive control. Schizophr Bull 35:115–135PubMedCrossRefGoogle Scholar
  19. Barch DM, Carter CS, Arnsten A, Buchanan RW, Cohen JD, Geyer M, Green MF, Krystal JH, Nuechterlein K, Robbins T, Silverstein S, Smith EE, Strauss M, Wykes T, Heinssen R (2009b) Selecting paradigms from cognitive neuroscience for translation into use in clinical trials: proceedings of the third CNTRICS meeting. Schizophr Bull 35:109–114PubMedCrossRefGoogle Scholar
  20. Barr AM, Lehmann-Masten V, Paulus M, Gainetdinov RR, Caron MG, Geyer MA (2004) The selective serotonin-2A receptor antagonist M100907 reverses behavioral deficits in dopamine transporter knockout mice. Neuropsychopharmacology 29:221–228PubMedCrossRefGoogle Scholar
  21. Basta-Kaim A, Fijal K, Budziszewska B, Regulska M, Leskiewicz M, Kubera M, Golembiowska K, Lason W, Wedzony K (2011) Prenatal lipopolysaccharide treatment enhances MK-801-induced psychotomimetic effects in rats. Pharmacol Biochem Behav 98:241–249PubMedCrossRefGoogle Scholar
  22. Baumeister AA, Francis JL (2002) Historical development of the dopamine hypothesis of schizophrenia. J Hist Neurosci 11:265–277PubMedCrossRefGoogle Scholar
  23. Becker A, Eyles DW, McGrath JJ, Grecksch G (2005) Transient prenatal vitamin D deficiency is associated with subtle alterations in learning and memory functions in adult rats. Behav Brain Res 161:306–312PubMedCrossRefGoogle Scholar
  24. Becker A, Grecksch G (2004) Ketamine-induced changes in rat behaviour: a possible animal model of schizophrenia Test of predictive validity. Prog Neuropsychopharmacol Biol Psychiatry 28:1267–1277PubMedCrossRefGoogle Scholar
  25. Becker A, Grecksch G, Bernstein HG, Hollt V, Bogerts B (1999) Social behaviour in rats lesioned with ibotenic acid in the hippocampus: quantitative and qualitative analysis. Psychopharmacology (Berl) 144:333–338CrossRefGoogle Scholar
  26. Becker A, Peters B, Schroeder H, Mann T, Huether G, Grecksch G (2003) Ketamine-induced changes in rat behaviour: a possible animal model of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 27:687–700PubMedCrossRefGoogle Scholar
  27. Benes FM (2000) Emerging principles of altered neural circuitry in schizophrenia. Brain Res Brain Res Rev 31:251–269PubMedCrossRefGoogle Scholar
  28. Benes FM, Berretta S (2001) GABAergic interneurons: implications for understanding schizophrenia and bipolar disorder. Neuropsychopharmacology 25:1–27PubMedCrossRefGoogle Scholar
  29. Bennay M, Gernert M, Schwabe K, Enkel T, Koch M (2004) Neonatal medial prefrontal cortex lesion enhances the sensitivity of the mesoaccumbal dopamine system. Eur J Neurosci 19:3277–3290PubMedCrossRefGoogle Scholar
  30. Bethus I, Lemaire V, Lhomme M, Goodall G (2005) Does prenatal stress affect latent inhibition? It depends on the gender. Behav Brain Res 158:331–338PubMedCrossRefGoogle Scholar
  31. Birkett P, Sigmundsson T, Sharma T, Toulopoulou T, Griffiths TD, Reveley A, Murray R (2007) Reaction time and sustained attention in schizophrenia and its genetic predisposition. Schizophr Res 95:76–85PubMedCrossRefGoogle Scholar
  32. Bitanihirwe BK, Peleg-Raibstein D, Mouttet F, Feldon J, Meyer U (2010) Late prenatal immune activation in mice leads to behavioral and neurochemical abnormalities relevant to the negative symptoms of schizophrenia. Neuropsychopharmacology 35:2462–2478PubMedCrossRefGoogle Scholar
  33. Bleuler E (1911) Dementia praecox or the groups of schizophrenias. International University Press, New York, NYGoogle Scholar
  34. Boksa P (2007) Of rats and schizophrenia. J Psychiatry Neurosci 32:8–10PubMedGoogle Scholar
  35. Boksa P, Krishnamurthy A, Brooks W (1995) Effects of a period of asphyxia during birth on spatial learning in the rat. Pediatr Res 37:489–496PubMedCrossRefGoogle Scholar
  36. Borgwardt SJ, Dickey C, Hulshoff Pol H, Whitford TJ, DeLisi LE (2009) Workshop on defining the significance of progressive brain change in schizophrenia: December 12, 2008 American College of Neuropsychopharmacology (ACNP) all-day satellite, Scottsdale Arizona. The rapporteurs’ report. Schizophr Res 112:32–45PubMedCrossRefGoogle Scholar
  37. Borrell J, Vela JM, Arevalo-Martin A, Molina-Holgado E, Guaza C (2002) Prenatal immune challenge disrupts sensorimotor gating in adult rats. Implications for the etiopathogenesis of schizophrenia. Neuropsychopharmacology 26:204–215PubMedCrossRefGoogle Scholar
  38. Bowie CR, Harvey PD (2006) Schizophrenia from a neuropsychiatric perspective. Mt Sinai J Med 73:993–998PubMedGoogle Scholar
  39. Brady AM, Saul RD, Wiest MK (2010) Selective deficits in spatial working memory in the neonatal ventral hippocampal lesion rat model of schizophrenia. Neuropharmacology 59:605–611PubMedCrossRefGoogle Scholar
  40. Braff DL, Geyer MA, Swerdlow NR (2001) Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies. Psychopharmacology (Berl) 156:234–258CrossRefGoogle Scholar
  41. Brake WG, Flores G, Francis D, Meaney MJ, Srivastava LK, Gratton A (2000) Enhanced nucleus accumbens dopamine and plasma corticosterone stress responses in adult rats with neonatal excitotoxic lesions to the medial prefrontal cortex. Neuroscience 96:687–695PubMedCrossRefGoogle Scholar
  42. Brioni JD, Keller EA, Levin LE, Cordoba N, Orsingher OA (1986) Reactivity to amphetamine in perinatally undernourished rats: behavioral and neurochemical correlates. Pharmacol Biochem Behav 24:449–454PubMedCrossRefGoogle Scholar
  43. Brody SA, Dulawa SC, Conquet F, Geyer MA (2004) Assessment of a prepulse inhibition deficit in a mutant mouse lacking mGlu5 receptors. Mol Psychiatry 9:35–41PubMedCrossRefGoogle Scholar
  44. Brown AS (2006) Prenatal infection as a risk factor for schizophrenia. Schizophr Bull 32:200–202PubMedCrossRefGoogle Scholar
  45. Brown AS (2008) The risk for schizophrenia from childhood and adult infections. Am J Psychiatry 165:7–10PubMedCrossRefGoogle Scholar
  46. Brown AS (2011) Further evidence of infectious insults in the pathogenesis and pathophysiology of schizophrenia. Am J Psychiatry 168:764–766PubMedCrossRefGoogle Scholar
  47. Brown AS, Derkits EJ (2010) Prenatal infection and schizophrenia: a review of epidemiologic and translational studies. Am J Psychiatry 167:261–280PubMedCrossRefGoogle Scholar
  48. Brown AS, Susser ES (2008) Prenatal nutritional deficiency and risk of adult schizophrenia. Schizophr Bull 34:1054–1063PubMedCrossRefGoogle Scholar
  49. Brown VJ, Bowman EM (2002) Rodent models of prefrontal cortical function. Trends Neurosci 25:340–343PubMedCrossRefGoogle Scholar
  50. Buchanan RW, Freedman R, Javitt DC, Abi-Dargham A, Lieberman JA (2007) Recent advances in the development of novel pharmacological agents for the treatment of cognitive impairments in schizophrenia. Schizophr Bull 33:1120–1130PubMedCrossRefGoogle Scholar
  51. Burne TH, Becker A, Brown J, Eyles DW, Mackay-Sim A, McGrath JJ (2004) Transient prenatal Vitamin D deficiency is associated with hyperlocomotion in adult rats. Behav Brain Res 154:549–555PubMedCrossRefGoogle Scholar
  52. Burne TH, O’Loan J, McGrath JJ, Eyles DW (2006) Hyperlocomotion associated with transient prenatal vitamin D deficiency is ameliorated by acute restraint. Behav Brain Res 174:119–124PubMedCrossRefGoogle Scholar
  53. Burton C, Lovic V, Fleming AS (2006) Early adversity alters attention and locomotion in adult Sprague-Dawley rats. Behav Neurosci 120:665–675PubMedCrossRefGoogle Scholar
  54. Cannon M, Jones PB, Murray RM (2002) Obstetric complications and schizophrenia: historical and meta-analytic review. Am J Psychiatry 159:1080–1092PubMedCrossRefGoogle Scholar
  55. Cardon M, Ron-Harel N, Cohen H, Lewitus GM, Schwartz M (2010) Dysregulation of kisspeptin and neurogenesis at adolescence link inborn immune deficits to the late onset of abnormal sensorimotor gating in congenital psychological disorders. Mol Psychiatry 15:415–425PubMedCrossRefGoogle Scholar
  56. Carlsson A, Waters N, Holm-Waters S, Tedroff J, Nilsson M, Carlsson ML (2001) Interactions between monoamines, glutamate, and GABA in schizophrenia: new evidence. Annu Rev Pharmacol Toxicol 41:237–260PubMedCrossRefGoogle Scholar
  57. Castagne V, Moser PC, Porsolt RD (2009) Preclinical behavioral models for predicting antipsychotic activity. Adv Pharmacol 57:381–418PubMedCrossRefGoogle Scholar
  58. Castner SA, Goldman-Rakic PS, Williams GV (2004) Animal models of working memory: insights for targeting cognitive dysfunction in schizophrenia. Psychopharmacology (Berl) 174:111–125CrossRefGoogle Scholar
  59. Ceaser AE, Goldberg TE, Egan MF, McMahon RP, Weinberger DR, Gold JM (2008) Set-shifting ability and schizophrenia: a marker of clinical illness or an intermediate phenotype? Biol Psychiatry 64:782–788PubMedCrossRefGoogle Scholar
  60. Chatterjee M, Ganguly S, Srivastava M, Palit G (2011) Effect of ‘chronic’ versus ‘acute’ ketamine administration and its ‘withdrawal’ effect on behavioural alterations in mice: implications for experimental psychosis. Behav Brain Res 216:247–254PubMedCrossRefGoogle Scholar
  61. Cirulli F, Berry A, Alleva E (2003) Early disruption of the mother-infant relationship: effects on brain plasticity and implications for psychopathology. Neurosci Biobehav Rev 27:73–82PubMedCrossRefGoogle Scholar
  62. Clapcote SJ, Lipina TV, Millar JK, Mackie S, Christie S, Ogawa F, Lerch JP, Trimble K, Uchiyama M, Sakuraba Y, Kaneda H, Shiroishi T, Houslay MD, Henkelman RM, Sled JG, Gondo Y, Porteous DJ, Roder JC (2007) Behavioral phenotypes of Disc1 missense mutations in mice. Neuron 54:387–402PubMedCrossRefGoogle Scholar
  63. Cook L, Tam SW, Rohrbach KW (1992) DuP 734 [1-(cyclopropylmethyl)-4-(2’(4”-fluorophenyl)-2’- oxoethyl)piperidine HBr], a potential antipsychotic agent: preclinical behavioral effects. J Pharmacol Exp Ther 263:1159–1166PubMedGoogle Scholar
  64. Coyle JT, Tsai G, Goff D (2003) Converging evidence of NMDA receptor hypofunction in the pathophysiology of schizophrenia. Ann N Y Acad Sci 1003:318–327PubMedCrossRefGoogle Scholar
  65. Coyle P, Tran N, Fung JN, Summers BL, Rofe AM (2009) Maternal dietary zinc supplementation prevents aberrant behaviour in an object recognition task in mice offspring exposed to LPS in early pregnancy. Behav Brain Res 197:210–218PubMedCrossRefGoogle Scholar
  66. Crawley JN (2007) Mouse behavioral assays relevant to the symptoms of autism. Brain Pathol 17:448–459PubMedCrossRefGoogle Scholar
  67. Crawley JN (2008) Behavioral phenotyping strategies for mutant mice. Neuron 57:809–818PubMedCrossRefGoogle Scholar
  68. Creese I, Iversen SD (1975) The pharmacological and anatomical substrates of the amphetamine response in the rat. Brain Res 83:419–436PubMedCrossRefGoogle Scholar
  69. Crider A (1997) Perseveration in schizophrenia. Schizophr Bull 23:63–74PubMedCrossRefGoogle Scholar
  70. Cronbach LJ, Meehl PE (1955) Construct validity in psychological tests. Psychol Bull 52:281–302PubMedCrossRefGoogle Scholar
  71. Daenen EW, Van der Heyden JA, Kruse CG, Wolterink G, Van Ree JM (2001) Adaptation and habituation to an open field and responses to various stressful events in animals with neonatal lesions in the amygdala or ventral hippocampus. Brain Res 918:153–165PubMedCrossRefGoogle Scholar
  72. Daenen EW, Wolterink G, Van Der Heyden JA, Kruse CG, Van Ree JM (2003) Neonatal lesions in the amygdala or ventral hippocampus disrupt prepulse inhibition of the acoustic startle response; implications for an animal model of neurodevelopmental disorders like schizophrenia. Eur Neuropsychopharmacol 13:187–197PubMedCrossRefGoogle Scholar
  73. Dalley JW, Cardinal RN, Robbins TW (2004) Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates. Neurosci Biobehav Rev 28:771–784PubMedCrossRefGoogle Scholar
  74. Dauer W, Przedborski S (2003) Parkinson’s disease: mechanisms and models. Neuron 39:889–909PubMedCrossRefGoogle Scholar
  75. Deakin JF, Simpson MD (1997) A two-process theory of schizophrenia: evidence from studies in post-mortem brain. J Psychiatr Res 31:277–295PubMedCrossRefGoogle Scholar
  76. Deminiere JM, Piazza PV, Guegan G, Abrous N, Maccari S, Le Moal M, Simon H (1992) Increased locomotor response to novelty and propensity to intravenous amphetamine self-administration in adult offspring of stressed mothers. Brain Res 586:135–139PubMedCrossRefGoogle Scholar
  77. Depoortere R, Dargazanli G, Estenne-Bouhtou G, Coste A, Lanneau C, Desvignes C, Poncelet M, Heaulme M, Santucci V, Decobert M, Cudennec A, Voltz C, Boulay D, Terranova JP, Stemmelin J, Roger P, Marabout B, Sevrin M, Vige X, Biton B, Steinberg R, Francon D, Alonso R, Avenet P, Oury-Donat F, Perrault G, Griebel G, George P, Soubrie P, Scatton B (2005) Neurochemical, electrophysiological and pharmacological profiles of the selective inhibitor of the glycine transporter-1 SSR504734, a potential new type of antipsychotic. Neuropsychopharmacology 30:1963–1985PubMedCrossRefGoogle Scholar
  78. Depoortere R, Perrault G, Sanger DJ (1997) Potentiation of prepulse inhibition of the startle reflex in rats: pharmacological evaluation of the procedure as a model for detecting antipsychotic activity. Psychopharmacology (Berl) 132:366–374CrossRefGoogle Scholar
  79. Desbonnet L, Waddington JL, O’Tuathaigh CM (2009) Mutant models for genes associated with schizophrenia. Biochem Soc Trans 37:308–312PubMedCrossRefGoogle Scholar
  80. Diaz R, Fuxe K, Ogren SO (1997) Prenatal corticosterone treatment induces long-term changes in spontaneous and apomorphine-mediated motor activity in male and female rats. Neuroscience 81:129–140PubMedCrossRefGoogle Scholar
  81. Diaz R, Ogren SO, Blum M, Fuxe K (1995) Prenatal corticosterone increases spontaneous and d-amphetamine induced locomotor activity and brain dopamine metabolism in prepubertal male and female rats. Neuroscience 66:467–473PubMedCrossRefGoogle Scholar
  82. Duncan GE, Moy SS, Lieberman JA, Koller BH (2006) Effects of haloperidol, clozapine, and quetiapine on sensorimotor gating in a genetic model of reduced NMDA receptor function. Psychopharmacology (Berl) 184:190–200CrossRefGoogle Scholar
  83. Eastwood SL, Lyon L, George L, Andrieux A, Job D, Harrison PJ (2007) Altered expression of synaptic protein mRNAs in STOP (MAP6) mutant mice. J Psychopharmacol 21:635–644PubMedCrossRefGoogle Scholar
  84. Eells JB, Misler JA, Nikodem VM (2006) Early postnatal isolation reduces dopamine levels, elevates dopamine turnover and specifically disrupts prepulse inhibition in Nurr1-null heterozygous mice. Neuroscience 140:1117–1126PubMedCrossRefGoogle Scholar
  85. 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 (Berl) 179:77–84CrossRefGoogle Scholar
  86. El-Khodor BF, Boksa P (1998) Birth insult increases amphetamine-induced behavioral responses in the adult rat. Neuroscience 87:893–904PubMedCrossRefGoogle Scholar
  87. Ellenbroek BA, Cools AR (2000a) Animal models for the negative symptoms of schizophrenia. Behav Pharmacol 11:223–233PubMedCrossRefGoogle Scholar
  88. Ellenbroek BA, Cools AR (2000b) The long-term effects of maternal deprivation depend on the genetic background. Neuropsychopharmacology 23:99–106PubMedCrossRefGoogle Scholar
  89. Elvevag B, Weinberger DR, Suter JC, Goldberg TE (2000) Continuous performance test and schizophrenia: a test of stimulus-response compatibility, working memory, response readiness, or none of the above? Am J Psychiatry 157:772–780PubMedCrossRefGoogle Scholar
  90. Enomoto T, Floresco SB (2009) Disruptions in spatial working memory, but not short-term memory, induced by repeated ketamine exposure. Prog Neuropsychopharmacol Biol Psychiatry 33:668–675PubMedCrossRefGoogle Scholar
  91. Eyles DW, Rogers F, Buller K, McGrath JJ, Ko P, French K, Burne TH (2006) Developmental vitamin D (DVD) deficiency in the rat alters adult behaviour independently of HPA function. Psychoneuroendocrinology 31:958–964PubMedCrossRefGoogle Scholar
  92. Featherstone RE, Kapur S, Fletcher PJ (2007a) The amphetamine-induced sensitized state as a model of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 31:1556–1571PubMedCrossRefGoogle Scholar
  93. Featherstone RE, Rizos Z, Kapur S, Fletcher PJ (2008) A sensitizing regimen of amphetamine that disrupts attentional set-shifting does not disrupt working or long-term memory. Behav Brain Res 189:170–179PubMedCrossRefGoogle Scholar
  94. Featherstone RE, Rizos Z, Nobrega JN, Kapur S, Fletcher PJ (2007b) Gestational methylazoxymethanol acetate treatment impairs select cognitive functions: parallels to schizophrenia. Neuropsychopharmacology 32:483–492PubMedCrossRefGoogle Scholar
  95. Feifel D, Shilling PD (2010) Promise and pitfalls of animal models of schizophrenia. Curr Psychiatry Rep 12:327–334PubMedCrossRefGoogle Scholar
  96. Feldon J, Weiner I (1992) From an animal model of an attentional deficit towards new insights into the pathophysiology of schizophrenia. J Psychiatr Res 26:345–366PubMedCrossRefGoogle Scholar
  97. Flagstad P, Glenthoj BY, Didriksen M (2005) Cognitive deficits caused by late gestational disruption of neurogenesis in rats: a preclinical model of schizophrenia. Neuropsychopharmacology 30:250–260PubMedCrossRefGoogle Scholar
  98. Flagstad P, Mork A, Glenthoj BY, van Beek J, Michael-Titus AT, Didriksen M (2004) Disruption of neurogenesis on gestational day 17 in the rat causes behavioral changes relevant to positive and negative schizophrenia symptoms and alters amphetamine-induced dopamine release in nucleus accumbens. Neuropsychopharmacology 29:2052–2064PubMedCrossRefGoogle Scholar
  99. Fletcher PJ, Tenn CC, Rizos Z, Lovic V, Kapur S (2005) Sensitization to amphetamine, but not PCP, impairs attentional set shifting: reversal by a D1 receptor agonist injected into the medial prefrontal cortex. Psychopharmacology (Berl) 183:190–200CrossRefGoogle Scholar
  100. Fletcher PJ, Tenn CC, Sinyard J, Rizos Z, Kapur S (2007) A sensitizing regimen of amphetamine impairs visual attention in the 5-choice serial reaction time test: reversal by a D1 receptor agonist injected into the medial prefrontal cortex. Neuropsychopharmacology 32:1122–1132PubMedCrossRefGoogle Scholar
  101. Floresco SB, Geyer MA, Gold LH, Grace AA (2005) Developing predictive animal models and establishing a preclinical trials network for assessing treatment effects on cognition in schizophrenia. Schizophr Bull 31:888–894PubMedCrossRefGoogle Scholar
  102. Fortier ME, Joober R, Luheshi GN, Boksa P (2004) Maternal exposure to bacterial endotoxin during pregnancy enhances amphetamine-induced locomotion and startle responses in adult rat offspring. J Psychiatr Res 38:335–345PubMedCrossRefGoogle Scholar
  103. Fortier ME, Luheshi GN, Boksa P (2007) Effects of prenatal infection on prepulse inhibition in the rat depend on the nature of the infectious agent and the stage of pregnancy. Behav Brain Res 181:270–277PubMedCrossRefGoogle Scholar
  104. Foussias G, Remington G (2010) Antipsychotics and schizophrenia: from efficacy and effectiveness to clinical decision-making. Can J Psychiatry 55:117–125PubMedGoogle Scholar
  105. Gainetdinov RR, Wetsel WC, Jones SR, Levin ED, Jaber M, Caron MG (1999) Role of serotonin in the paradoxical calming effect of psychostimulants on hyperactivity. Science 283:397–401PubMedCrossRefGoogle Scholar
  106. Gal G, Joel D, Gusak O, Feldon J, Weiner I (1997) The effects of electrolytic lesion to the shell subterritory of the nucleus accumbens on delayed non-matching-to-sample and four-arm baited eight-arm radial-maze tasks. Behav Neurosci 111:92–103PubMedCrossRefGoogle Scholar
  107. Garner JP, Thogerson CM, Wurbel H, Murray JD, Mench JA (2006) Animal neuropsychology: validation of the Intra-Dimensional Extra-Dimensional set shifting task for mice. Behav Brain Res 173:53–61PubMedCrossRefGoogle Scholar
  108. Gerdjikov TV, Rudolph U, Keist R, Mohler H, Feldon J, Yee BK (2008) Hippocampal alpha 5 subunit-containing GABA A receptors are involved in the development of the latent inhibition effect. Neurobiol Learn Mem 89:87–94PubMedCrossRefGoogle Scholar
  109. Geyer MA (2006) The family of sensorimotor gating disorders: comorbidities or diagnostic overlaps? Neurotox Res 10:211–220PubMedCrossRefGoogle Scholar
  110. Geyer MA (2008) Developing translational animal models for symptoms of schizophrenia or bipolar mania. Neurotox Res 14:71–78PubMedCrossRefGoogle Scholar
  111. Geyer MA, Krebs-Thomson K, Braff DL, Swerdlow NR (2001) Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review. Psychopharmacology (Berl) 156:117–154CrossRefGoogle Scholar
  112. Giros B, Jaber M, Jones SR, Wightman RM, Caron MG (1996) Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature 379:606–612PubMedCrossRefGoogle Scholar
  113. Gogos JA, Gerber DJ (2006) Schizophrenia susceptibility genes: emergence of positional candidates and future directions. Trends Pharmacol Sci 27:226–233PubMedCrossRefGoogle Scholar
  114. Gogos JA, Morgan M, Luine V, Santha M, Ogawa S, Pfaff D, Karayiorgou M (1998) Catechol-O-methyltransferase-deficient mice exhibit sexually dimorphic changes in catecholamine levels and behavior. Proc Natl Acad Sci USA 95:9991–9996PubMedCrossRefGoogle Scholar
  115. Golan HM, Lev V, Hallak M, Sorokin Y, Huleihel M (2005) Specific neurodevelopmental damage in mice offspring following maternal inflammation during pregnancy. Neuropharmacology 48:903–917PubMedCrossRefGoogle Scholar
  116. Goldman-Rakic PS (1994) Working memory dysfunction in schizophrenia. J Neuropsychiatry Clin Neurosci 6:348–357PubMedGoogle Scholar
  117. Gottesman II, Gould TD (2003) The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 160:636–645PubMedCrossRefGoogle Scholar
  118. Gould TD, Gottesman II (2006) Psychiatric endophenotypes and the development of valid animal models. Genes Brain Behav 5:113–119PubMedCrossRefGoogle Scholar
  119. Gray L, van den Buuse M, Scarr E, Dean B, Hannan AJ (2009) Clozapine reverses schizophrenia-related behaviours in the metabotropic glutamate receptor 5 knockout mouse: association with N-methyl-D-aspartic acid receptor up-regulation. Int J Neuropsychopharmacol 12:45–60PubMedCrossRefGoogle Scholar
  120. Grecksch G, Bernstein HG, Becker A, Hollt V, Bogerts B (1999) Disruption of latent inhibition in rats with postnatal hippocampal lesions. Neuropsychopharmacology 20:525–532PubMedCrossRefGoogle Scholar
  121. Green MF, Nuechterlein KH, Gold JM, Barch DM, Cohen J, Essock S, Fenton WS, Frese F, Goldberg TE, Heaton RK, Keefe RS, Kern RS, Kraemer H, Stover E, Weinberger DR, Zalcman S, Marder SR (2004) Approaching a consensus cognitive battery for clinical trials in schizophrenia: the NIMH-MATRICS conference to select cognitive domains and test criteria. Biol Psychiatry 56:301–307PubMedCrossRefGoogle Scholar
  122. Gue M, Bravard A, Meunier J, Veyrier R, Gaillet S, Recasens M, Maurice T (2004) Sex differences in learning deficits induced by prenatal stress in juvenile rats. Behav Brain Res 150:149–157PubMedCrossRefGoogle Scholar
  123. Guo X, Hamilton PJ, Reish NJ, Sweatt JD, Miller CA, Rumbaugh G (2009) Reduced expression of the NMDA receptor-interacting protein SynGAP causes behavioral abnormalities that model symptoms of Schizophrenia. Neuropsychopharmacology 34:1659–1672PubMedCrossRefGoogle Scholar
  124. Hanlon FM, Sutherland RJ (2000) Changes in adult brain and behavior caused by neonatal limbic damage: implications for the etiology of schizophrenia. Behav Brain Res 107:71–83PubMedCrossRefGoogle Scholar
  125. Harrison PJ (1999) The neuropathology of schizophrenia. A critical review of the data and their interpretation. Brain 122:593–624PubMedCrossRefGoogle Scholar
  126. Harrison PJ (2004) The hippocampus in schizophrenia: a review of the neuropathological evidence and its pathophysiological implications. Psychopharmacology (Berl) 174:151–162CrossRefGoogle Scholar
  127. Harrison PJ, Weinberger DR (2005) Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol Psychiatry 10:40–68PubMedCrossRefGoogle Scholar
  128. Hauser J, Feldon J, Pryce CR (2006) Prenatal dexamethasone exposure, postnatal development, and adulthood prepulse inhibition and latent inhibition in Wistar rats. Behav Brain Res 175:51–61PubMedCrossRefGoogle Scholar
  129. Hauser J, Feldon J, Pryce CR (2009) Direct and dam-mediated effects of prenatal dexamethasone on emotionality, cognition and HPA axis in adult Wistar rats. Horm Behav 56:364–375PubMedCrossRefGoogle Scholar
  130. Hauser J, Rudolph U, Keist R, Mohler H, Feldon J, Yee BK (2005) Hippocampal alpha5 subunit-containing GABAA receptors modulate the expression of prepulse inhibition. Mol Psychiatry 10:201–207PubMedCrossRefGoogle Scholar
  131. Hazane F, Krebs MO, Jay TM, Le Pen G (2009) Behavioral perturbations after prenatal neurogenesis disturbance in female rat. Neurotox Res 15:311–320PubMedCrossRefGoogle Scholar
  132. Henry C, Guegant G, Cador M, Arnauld E, Arsaut J, Le Moal M, Demotes-Mainard J (1995) Prenatal stress in rats facilitates amphetamine-induced sensitization and induces long-lasting changes in dopamine receptors in the nucleus accumbens. Brain Res 685:179–186PubMedCrossRefGoogle Scholar
  133. Hikida T, Jaaro-Peled H, Seshadri S, Oishi K, Hookway C, Kong S, Wu D, Xue R, Andrade M, Tankou S, Mori S, Gallagher M, Ishizuka K, Pletnikov M, Kida S, Sawa A (2007) Dominant-negative DISC1 transgenic mice display schizophrenia-associated phenotypes detected by measures translatable to humans. Proc Natl Acad Sci USA 104:14501–14506PubMedCrossRefGoogle Scholar
  134. Hill SK, Bishop JR, Palumbo D, Sweeney JA (2010) Effect of second-generation antipsychotics on cognition: current issues and future challenges. Expert Rev Neurother 10:43–57PubMedCrossRefGoogle Scholar
  135. Howes OD, Kapur S (2009) The dopamine hypothesis of schizophrenia: version III–the final common pathway. Schizophr Bull 35:549–562PubMedCrossRefGoogle Scholar
  136. Hughes B (2009) Novel consortium to address shortfall in innovative medicines for psychiatric disorders. Nat Rev Drug Discov 8:523–524PubMedCrossRefGoogle Scholar
  137. Huotari M, Santha M, Lucas LR, Karayiorgou M, Gogos JA, Mannisto PT (2002) Effect of dopamine uptake inhibition on brain catecholamine levels and locomotion in catechol-O-methyltransferase-disrupted mice. J Pharmacol Exp Ther 303:1309–1316PubMedCrossRefGoogle Scholar
  138. Javitt DC (2007) Glutamate and schizophrenia: phencyclidine, N-methyl-D-aspartate receptors, and dopamine-glutamate interactions. Int Rev Neurobiol 78:69–108PubMedCrossRefGoogle Scholar
  139. Jentsch JD, Roth RH (1999) The neuropsychopharmacology of phencyclidine: from NMDA receptor hypofunction to the dopamine hypothesis of schizophrenia. Neuropsychopharmacology 20:201–225PubMedCrossRefGoogle Scholar
  140. Joel D, Weiner I, Feldon J (1997) Electrolytic lesions of the medial prefrontal cortex in rats disrupt performance on an analog of the Wisconsin Card Sorting Test, but do not disrupt latent inhibition: implications for animal models of schizophrenia. Behav Brain Res 85:187–201PubMedCrossRefGoogle Scholar
  141. Jones SH, Gray JA, Hemsley DR (1992) Loss of the Kamin blocking effect in acute but not chronic schizophrenics. Biol Psychiatry 32:739–755PubMedCrossRefGoogle Scholar
  142. Jongen-Rêlo AL, Leng A, Luber M, Pothuizen HH, Weber L, Feldon J (2004) The prenatal methylazoxymethanol acetate treatment: a neurodevelopmental animal model for schizophrenia? Behav Brain Res 149:159–181PubMedCrossRefGoogle Scholar
  143. Kantrowitz JT, Javitt DC (2010) Thinking glutamatergically: changing concepts of schizophrenia based upon changing neurochemical models. Clin Schizophr Relat Psychoses 4:189–200PubMedCrossRefGoogle Scholar
  144. Karlsson RM, Tanaka K, Heilig M, Holmes A (2008) 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 Psychiatry 64:810–814PubMedCrossRefGoogle Scholar
  145. Karlsson RM, Tanaka K, Saksida LM, Bussey TJ, Heilig M, Holmes A (2009) Assessment of glutamate transporter GLAST (EAAT1)-deficient mice for phenotypes relevant to the negative and executive/cognitive symptoms of schizophrenia. Neuropsychopharmacology 34:1578–1589PubMedCrossRefGoogle Scholar
  146. Kellendonk C, Simpson EH, Kandel ER (2009) Modeling cognitive endophenotypes of schizophrenia in mice. Trends Neurosci 32:347–358PubMedCrossRefGoogle Scholar
  147. Kellendonk C, Simpson EH, Polan HJ, Malleret G, Vronskaya S, Winiger V, Moore H, Kandel ER (2006) Transient and selective overexpression of dopamine D2 receptors in the striatum causes persistent abnormalities in prefrontal cortex functioning. Neuron 49:603–615PubMedCrossRefGoogle Scholar
  148. Kesby JP, Burne TH, McGrath JJ, Eyles DW (2006) Developmental vitamin D deficiency alters MK 801-induced hyperlocomotion in the adult rat: an animal model of schizophrenia. Biol Psychiatry 60:591–596PubMedCrossRefGoogle Scholar
  149. Kim Y, Zerwas S, Trace SE, Sullivan PF (2011) Schizophrenia genetics: where next? Schizophr Bull 37:456–463PubMedCrossRefGoogle Scholar
  150. Kodsi MH, Swerdlow NR (1994) Quinolinic acid lesions of the ventral striatum reduce sensorimotor gating of acoustic startle in rats. Brain Res 643:59–65PubMedCrossRefGoogle Scholar
  151. Koenig JI, Elmer GI, Shepard PD, Lee PR, Mayo C, Joy B, Hercher E, Brady DL (2005) Prenatal exposure to a repeated variable stress paradigm elicits behavioral and neuroendocrinological changes in the adult offspring: potential relevance to schizophrenia. Behav Brain Res 156:251–261PubMedCrossRefGoogle Scholar
  152. Koike H, Arguello PA, Kvajo M, Karayiorgou M, Gogos JA (2006) Disc1 is mutated in the 129S6/SvEv strain and modulates working memory in mice. Proc Natl Acad Sci USA 103:3693–3697PubMedCrossRefGoogle Scholar
  153. Kokkinidis L, Anisman H (1981) Amphetamine psychosis and schizophrenia: a dual model. Neurosci Biobehav Rev 5:449–461PubMedCrossRefGoogle Scholar
  154. Kraepelin E (1919) Dementia praecox and paraphrenia. Kreiger, New York, NYGoogle Scholar
  155. Krueger DD, Howell JL, Hebert BF, Olausson P, Taylor JR, Nairn AC (2006) Assessment of cognitive function in the heterozygous reeler mouse. Psychopharmacology (Berl) 189:95–104CrossRefGoogle Scholar
  156. Kvajo M, McKellar H, Arguello PA, Drew LJ, Moore H, MacDermott AB, Karayiorgou M, Gogos JA (2008) A mutation in mouse Disc1 that models a schizophrenia risk allele leads to specific alterations in neuronal architecture and cognition. Proc Natl Acad Sci USA 105:7076–7081PubMedCrossRefGoogle Scholar
  157. Kvajo M, McKellar H, Gogos JA (2012) Avoiding mouse traps in schizophrenia genetics: lessons and promises from current and emerging mouse models. Neuroscience 211:136–164PubMedCrossRefGoogle Scholar
  158. Labrie V, Lipina T, Roder JC (2008) Mice with reduced NMDA receptor glycine affinity model some of the negative and cognitive symptoms of schizophrenia. Psychopharmacology (Berl) 200:217–230CrossRefGoogle Scholar
  159. Lacroix L, Broersen LM, Weiner I, Feldon J (1998) The effects of excitotoxic lesion of the medial prefrontal cortex on latent inhibition, prepulse inhibition, food hoarding, elevated plus maze, active avoidance and locomotor activity in the rat. Neuroscience 84:431–442PubMedCrossRefGoogle Scholar
  160. Lacroix L, Spinelli S, White W, Feldon J (2000) The effects of ibotenic acid lesions of the medial and lateral prefrontal cortex on latent inhibition, prepulse inhibition and amphetamine-induced hyperlocomotion. Neuroscience 97:459–468PubMedCrossRefGoogle Scholar
  161. Langston JW, Ballard P (1984) Parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): implications for treatment and the pathogenesis of Parkinson’s disease. Can J Neurol Sci 11:160–165PubMedGoogle Scholar
  162. Laruelle M (2000) The role of endogenous sensitization in the pathophysiology of schizophrenia: implications from recent brain imaging studies. Brain Res Brain Res Rev 31:371–384PubMedCrossRefGoogle Scholar
  163. Laruelle M, Abi-Dargham A (1999) Dopamine as the wind of the psychotic fire: new evidence from brain imaging studies. J Psychopharmacol 13:358–371PubMedCrossRefGoogle Scholar
  164. Laruelle M, Abi-Dargham A, van Dyck CH, Gil R, D’Souza CD, Erdos J, McCance E, Rosenblatt W, Fingado C, Zoghbi SS, Baldwin RM, Seibyl JP, Krystal JH, Charney DS, Innis RB (1996) Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. Proc Natl Acad Sci USA 93:9235–9240PubMedCrossRefGoogle Scholar
  165. Laruelle M, Kegeles LS, Abi-Dargham A (2003) Glutamate, dopamine, and schizophrenia: from pathophysiology to treatment. Ann N Y Acad Sci 1003:138–158PubMedCrossRefGoogle Scholar
  166. Laurent A, Biloa-Tang M, Bougerol T, Duly D, Anchisi AM, Bosson JL, Pellat J, d’Amato T, Dalery J (2000) Executive/attentional performance and measures of schizotypy in patients with schizophrenia and in their nonpsychotic first-degree relatives. Schizophr Res 46:269–283PubMedCrossRefGoogle Scholar
  167. Laurent A, Saoud M, Bougerol T, d’Amato T, Anchisi AM, Biloa-Tang M, Dalery J, Rochet T (1999) Attentional deficits in patients with schizophrenia and in their non-psychotic first-degree relatives. Psychiatry Res 89:147–159PubMedCrossRefGoogle Scholar
  168. Laviola G, Ognibene E, Romano E, Adriani W, Keller F (2009) Gene-environment interaction during early development in the heterozygous reeler mouse: clues for modelling of major neurobehavioral syndromes. Neurosci Biobehav Rev 33:560–572PubMedCrossRefGoogle Scholar
  169. Le Pen G, Gourevitch R, Hazane F, Hoareau C, Jay TM, Krebs MO (2006) Peri-pubertal maturation after developmental disturbance: a model for psychosis onset in the rat. Neuroscience 143:395–405PubMedCrossRefGoogle Scholar
  170. Le Pen G, Grottick AJ, Higgins GA, Moreau JL (2003) Phencyclidine exacerbates attentional deficits in a neurodevelopmental rat model of schizophrenia. Neuropsychopharmacology 28:1799–1809PubMedCrossRefGoogle Scholar
  171. Le Pen G, Moreau JL (2002) Disruption of prepulse inhibition of startle reflex in a neurodevelopmental model of schizophrenia: reversal by clozapine, olanzapine and risperidone but not by haloperidol. Neuropsychopharmacology 27:1–11PubMedCrossRefGoogle Scholar
  172. Lee PR, Brady DL, Shapiro RA, Dorsa DM, Koenig JI (2005) Social interaction deficits caused by chronic phencyclidine administration are reversed by oxytocin. Neuropsychopharmacology 30:1883–1894PubMedCrossRefGoogle Scholar
  173. Lee PR, Brady DL, Shapiro RA, Dorsa DM, Koenig JI (2007) Prenatal stress generates deficits in rat social behavior: reversal by oxytocin. Brain Res 1156:152–167PubMedCrossRefGoogle Scholar
  174. Lehmann J, Stohr T, Feldon J (2000) Long-term effects of prenatal stress experiences and postnatal maternal separation on emotionality and attentional processes. Behav Brain Res 107:133–144PubMedCrossRefGoogle Scholar
  175. Leng A, Jongen-Rêlo AL, Pothuizen HH, Feldon J (2005) Effects of prenatal methylazoxymethanol acetate (MAM) treatment in rats on water maze performance. Behav Brain Res 161:291–298PubMedCrossRefGoogle Scholar
  176. Lesch KP (1999) Gene transfer to the brain: emerging therapeutic strategy in psychiatry? Biol Psychiatry 45:247–253PubMedCrossRefGoogle Scholar
  177. Lewis DA, Hashimoto T, Volk DW (2005) Cortical inhibitory neurons and schizophrenia. Nat Rev Neurosci 6:312–324PubMedCrossRefGoogle Scholar
  178. Lewis DA, Pierri JN, Volk DW, Melchitzky DS, Woo TU (1999) Altered GABA neurotransmission and prefrontal cortical dysfunction in schizophrenia. Biol Psychiatry 46:616–626PubMedCrossRefGoogle Scholar
  179. Li Q, Cheung C, Wei R, Hui ES, Feldon J, Meyer U, Chung S, Chua SE, Sham PC, Wu EX, McAlonan GM (2009) Prenatal immune challenge is an environmental risk factor for brain and behavior change relevant to schizophrenia: evidence from MRI in a mouse model. PLoS One 4:e6354PubMedCrossRefGoogle Scholar
  180. Li W, Zhou Y, Jentsch JD, Brown RA, Tian X, Ehninger D, Hennah W, Peltonen L, Lonnqvist J, Huttunen MO, Kaprio J, Trachtenberg JT, Silva AJ, Cannon TD (2007) Specific developmental disruption of disrupted-in-schizophrenia-1 function results in schizophrenia-related phenotypes in mice. Proc Natl Acad Sci USA 104:18280–18285PubMedCrossRefGoogle Scholar
  181. Lieberman JA, Kane JM, Alvir J (1987) Provocative tests with psychostimulant drugs in schizophrenia. Psychopharmacology (Berl) 91:415–433CrossRefGoogle Scholar
  182. Lieberman JA, Sheitman BB, Kinon BJ (1997) Neurochemical sensitization in the pathophysiology of schizophrenia: deficits and dysfunction in neuronal regulation and plasticity. Neuropsychopharmacology 17:205–229PubMedCrossRefGoogle Scholar
  183. Lillrank SM, Lipska BK, Weinberger DR (1995) Neurodevelopmental animal models of schizophrenia. Clin Neurosci 3:98–104PubMedGoogle Scholar
  184. Lipina T, Weiss K, Roder J (2007) The ampakine CX546 restores the prepulse inhibition and latent inhibition deficits in mGluR5-deficient mice. Neuropsychopharmacology 32:745–756PubMedCrossRefGoogle Scholar
  185. Lipska BK (2004) Using animal models to test a neurodevelopmental hypothesis of schizophrenia. J Psychiatry Neurosci 29:282–286PubMedGoogle Scholar
  186. Lipska BK, al-Amin HA, Weinberger DR (1998) Excitotoxic lesions of the rat medial prefrontal cortex. Effects on abnormal behaviors associated with neonatal hippocampal damage. Neuropsychopharmacology 19:451–464PubMedCrossRefGoogle Scholar
  187. Lipska BK, Aultman JM, Verma A, Weinberger DR, Moghaddam B (2002) Neonatal damage of the ventral hippocampus impairs working memory in the rat. Neuropsychopharmacology 27:47–54PubMedCrossRefGoogle Scholar
  188. Lipska BK, Jaskiw GE, Weinberger DR (1993) Postpubertal emergence of hyperresponsiveness to stress and to amphetamine after neonatal excitotoxic hippocampal damage: a potential animal model of schizophrenia. Neuropsychopharmacology 9:67–75PubMedGoogle Scholar
  189. Lipska BK, Swerdlow NR, Geyer MA, Jaskiw GE, Braff DL, Weinberger DR (1995) Neonatal excitotoxic hippocampal damage in rats causes post-pubertal changes in prepulse inhibition of startle and its disruption by apomorphine. Psychopharmacology (Berl) 122:35–43CrossRefGoogle Scholar
  190. Lipska BK, Weinberger DR (1994) Subchronic treatment with haloperidol and clozapine in rats with neonatal excitotoxic hippocampal damage. Neuropsychopharmacology 10:199–205PubMedGoogle Scholar
  191. Lipska BK, Weinberger DR (2000) To model a psychiatric disorder in animals: schizophrenia as a reality test. Neuropsychopharmacology 23:223–239PubMedCrossRefGoogle Scholar
  192. Lipska BK, Weinberger DR (2002) A neurodevelopmental model of schizophrenia: neonatal disconnection of the hippocampus. Neurotox Res 4:469–475PubMedCrossRefGoogle Scholar
  193. Lodge DJ, Grace AA (2009) Gestational methylazoxymethanol acetate administration: a developmental disruption model of schizophrenia. Behav Brain Res 204:306–312PubMedCrossRefGoogle Scholar
  194. Low NC, Hardy J (2007) What is a schizophrenic mouse? Neuron 54:348–349PubMedCrossRefGoogle Scholar
  195. Lubow RE (2005) Construct validity of the animal latent inhibition model of selective attention deficits in schizophrenia. Schizophr Bull 31:139–153PubMedCrossRefGoogle Scholar
  196. Makinodan M, Tatsumi K, Manabe T, Yamauchi T, Makinodan E, Matsuyoshi H, Shimoda S, Noriyama Y, Kishimoto T, Wanaka A (2008) Maternal immune activation in mice delays myelination and axonal development in the hippocampus of the offspring. J Neurosci Res 86:2190–2200PubMedCrossRefGoogle Scholar
  197. Mansbach RS, Geyer MA (1989) Effects of phencyclidine and phencyclidine biologs on sensorimotor gating in the rat. Neuropsychopharmacology 2:299–308PubMedCrossRefGoogle Scholar
  198. Mansbach RS, Geyer MA, Braff DL (1988) Dopaminergic stimulation disrupts sensorimotor gating in the rat. Psychopharmacology (Berl) 94:507–514CrossRefGoogle Scholar
  199. Marder SR (2006) Initiatives to promote the discovery of drugs to improve cognitive function in severe mental illness. J Clin Psychiatry 67:e03PubMedCrossRefGoogle Scholar
  200. Marighetto A, Yee BK, Rawlins JN (1998) The effects of cytotoxic entorhinal lesions and electrolytic medial septal lesions on the acquisition and retention of a spatial working memory task. Exp Brain Res 119:517–528PubMedCrossRefGoogle Scholar
  201. Markham JA, Taylor AR, Taylor SB, Bell DB, Koenig JI (2010) Characterization of the cognitive impairments induced by prenatal exposure to stress in the rat. Front Behav Neurosci 4:173PubMedCrossRefGoogle Scholar
  202. Markou A, Chiamulera C, Geyer MA, Tricklebank M, Steckler T (2009) Removing obstacles in neuroscience drug discovery: the future path for animal models. Neuropsychopharmacology 34:74–89PubMedCrossRefGoogle Scholar
  203. Martin LF, Freedman R (2007) Schizophrenia and the alpha7 nicotinic acetylcholine receptor. Int Rev Neurobiol 78:225–246PubMedCrossRefGoogle Scholar
  204. McDonald C, Murray RM (2000) Early and late environmental risk factors for schizophrenia. Brain Res Brain Res Rev 31:130–137PubMedCrossRefGoogle Scholar
  205. McGlashan TH, Fenton WS (1992) The positive-negative distinction in schizophrenia. Review of natural history validators. Arch Gen Psychiatry 49:63–72PubMedCrossRefGoogle Scholar
  206. Meunier J, Gue M, Recasens M, Maurice T (2004) Attenuation by a sigma1 (sigma1) receptor agonist of the learning and memory deficits induced by a prenatal restraint stress in juvenile rats. Br J Pharmacol 142:689–700PubMedCrossRefGoogle Scholar
  207. Meyer U, Engler A, Weber L, Schedlowski M, Feldon J (2008a) Preliminary evidence for a modulation of fetal dopaminergic development by maternal immune activation during pregnancy. Neuroscience 154:701–709PubMedCrossRefGoogle Scholar
  208. Meyer U, Feldon J (2010) Epidemiology-driven neurodevelopmental animal models of schizophrenia. Prog Neurobiol 90:285–326PubMedCrossRefGoogle Scholar
  209. Meyer U, Feldon J, Schedlowski M, Yee BK (2005) Towards an immuno-precipitated neurodevelopmental animal model of schizophrenia. Neurosci Biobehav Rev 29:913–947PubMedCrossRefGoogle Scholar
  210. Meyer U, Feldon J, Schedlowski M, Yee BK (2006a) Immunological stress at the maternal-foetal interface: a link between neurodevelopment and adult psychopathology. Brain Behav Immun 20:378–388PubMedCrossRefGoogle Scholar
  211. Meyer U, Knuesel I, Nyffeler M, Feldon J (2010) Chronic clozapine treatment improves prenatal infection-induced working memory deficits without influencing adult hippocampal neurogenesis. Psychopharmacology (Berl) 208:531–543CrossRefGoogle Scholar
  212. Meyer U, Nyffeler M, Engler A, Urwyler A, Schedlowski M, Knuesel I, Yee BK, Feldon J (2006b) The time of prenatal immune challenge determines the specificity of inflammation-mediated brain and behavioral pathology. J Neurosci 26:4752–4762PubMedCrossRefGoogle Scholar
  213. Meyer U, Nyffeler M, Schwendener S, Knuesel I, Yee BK, Feldon J (2008b) Relative prenatal and postnatal maternal contributions to schizophrenia-related neurochemical dysfunction after in utero immune challenge. Neuropsychopharmacology 33:441–456PubMedCrossRefGoogle Scholar
  214. Meyer U, Nyffeler M, Yee BK, Knuesel I, Feldon J (2008c) Adult brain and behavioral pathological markers of prenatal immune challenge during early/middle and late fetal development in mice. Brain Behav Immun 22:469–486PubMedCrossRefGoogle Scholar
  215. Meyer U, Schwendener S, Feldon J, Yee BK (2006c) Prenatal and postnatal maternal contributions in the infection model of schizophrenia. Exp Brain Res 173:243–257PubMedCrossRefGoogle Scholar
  216. Mohn AR, Gainetdinov RR, Caron MG, Koller BH (1999) Mice with reduced NMDA receptor expression display behaviors related to schizophrenia. Cell 98:427–436PubMedCrossRefGoogle Scholar
  217. Möller HJ (2004) Course and long-term treatment of schizophrenic psychoses. Pharmacopsychiatry 37(Suppl 2):126–135PubMedCrossRefGoogle Scholar
  218. Moore H (2010) The role of rodent models in the discovery of new treatments for schizophrenia: updating our strategy. Schizophr Bull 36:1066–1072PubMedCrossRefGoogle Scholar
  219. Moore H, Jentsch JD, Ghajarnia M, Geyer MA, Grace AA (2006) A neurobehavioral systems analysis of adult rats exposed to methylazoxymethanol acetate on E17: implications for the neuropathology of schizophrenia. Biol Psychiatry 60:253–264PubMedCrossRefGoogle Scholar
  220. Moran PM, Al-Uzri MM, Watson J, Reveley MA (2003) Reduced Kamin blocking in non paranoid schizophrenia: associations with schizotypy. J Psychiatr Res 37:155–163PubMedCrossRefGoogle Scholar
  221. Moran PM, Owen L, Crookes AE, Al-Uzri MM, Reveley MA (2008) Abnormal prediction error is associated with negative and depressive symptoms in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 32:116–123PubMedCrossRefGoogle Scholar
  222. Moreno JL, Kurita M, Holloway T, Lopez J, Cadagan R, Martinez-Sobrido L, Garcia-Sastre A, Gonzalez-Maeso J (2011) Maternal influenza viral infection causes schizophrenia-like alterations of 5-HTA and mGlu receptors in the adult offspring. J Neurosci 31:1863–1872PubMedCrossRefGoogle Scholar
  223. Morrens M, Hulstijn W, Lewi PJ, De Hert M, Sabbe BG (2006) Stereotypy in schizophrenia. Schizophr Res 84:397–404PubMedCrossRefGoogle Scholar
  224. Moser PC, Hitchcock JM, Lister S, Moran PM (2000) The pharmacology of latent inhibition as an animal model of schizophrenia. Brain Res Brain Res Rev 33:275–307PubMedCrossRefGoogle Scholar
  225. Mouri A, Noda Y, Enomoto T, Nabeshima T (2007) Phencyclidine animal models of schizophrenia: approaches from abnormality of glutamatergic neurotransmission and neurodevelopment. Neurochem Int 51:173–184PubMedCrossRefGoogle Scholar
  226. Moy SS, Perez A, Koller BH, Duncan GE (2006) Amphetamine-induced disruption of prepulse inhibition in mice with reduced NMDA receptor function. Brain Res 1089:186–194PubMedCrossRefGoogle Scholar
  227. Murphy CA, Fend M, Russig H, Feldon J (2001) Latent inhibition, but not prepulse inhibition, is reduced during withdrawal from an escalating dosage schedule of amphetamine. Behav Neurosci 115:1247–1256PubMedCrossRefGoogle Scholar
  228. Murray GK, Cheng F, Clark L, Barnett JH, Blackwell AD, Fletcher PC, Robbins TW, Bullmore ET, Jones PB (2008) Reinforcement and reversal learning in first-episode psychosis. Schizophr Bull 34:848–855PubMedCrossRefGoogle Scholar
  229. Nabeshima T, Kozawa T, Furukawa H, Kameyama T (1986) Phencyclidine-induced retrograde amnesia in mice. Psychopharmacology (Berl) 89:334–337CrossRefGoogle Scholar
  230. Nabeshima T, Mouri A, Murai R, Noda Y (2006) Animal model of schizophrenia: dysfunction of NMDA receptor-signaling in mice following withdrawal from repeated administration of phencyclidine. Ann N Y Acad Sci 1086:160–168PubMedCrossRefGoogle Scholar
  231. Nelson EE, Winslow JT (2009) Non-human primates: model animals for developmental psychopathology. Neuropsychopharmacology 34:90–105PubMedCrossRefGoogle Scholar
  232. Nestler EJ, Hyman SE (2010) Animal models of neuropsychiatric disorders. Nat Neurosci 13:1161–1169PubMedCrossRefGoogle Scholar
  233. Nieratschker V, Nothen MM, Rietschel M (2010) New genetic findings in schizophrenia: Is there still room for the dopamine hypothesis of schizophrenia? Front Behav Neurosci 4:23PubMedGoogle Scholar
  234. Nuechterlein KH, Luck SJ, Lustig C, Sarter M (2009) CNTRICS final task selection: control of attention. Schizophr Bull 35:182–196PubMedCrossRefGoogle Scholar
  235. O’Connell G, Lawrie SM, McIntosh AM, Hall J (2011) Schizophrenia risk genes: implications for future drug development and discovery. Biochem Pharmacol 81:1367–1373PubMedCrossRefGoogle Scholar
  236. O’Loan J, Eyles DW, Kesby J, Ko P, McGrath JJ, Burne TH (2007) Vitamin D deficiency during various stages of pregnancy in the rat; its impact on development and behaviour in adult offspring. Psychoneuroendocrinology 32:227–234PubMedCrossRefGoogle Scholar
  237. Oswald CJ, Yee BK, Rawlins JN, Bannerman DB, Good M, Honey RC (2002) The influence of selective lesions to components of the hippocampal system on the orienting [correction of orientating] response, habituation and latent inhibition. Eur J Neurosci 15:1983–1990PubMedCrossRefGoogle Scholar
  238. Ouagazzal AM, Jenck F, Moreau JL (2001) Drug-induced potentiation of prepulse inhibition of acoustic startle reflex in mice: a model for detecting antipsychotic activity? Psychopharmacology (Berl) 156:273–283CrossRefGoogle Scholar
  239. Ozawa K, Hashimoto K, Kishimoto T, Shimizu E, Ishikura H, Iyo M (2006) Immune activation during pregnancy in mice leads to dopaminergic hyperfunction and cognitive impairment in the offspring: a neurodevelopmental animal model of schizophrenia. Biol Psychiatry 59:546–554PubMedCrossRefGoogle Scholar
  240. Paine TA, Carlezon WA Jr (2009) Effects of antipsychotic drugs on MK-801-induced attentional and motivational deficits in rats. Neuropharmacology 56:788–797PubMedCrossRefGoogle Scholar
  241. Palmer AA, Brown AS, Keegan D, Siska LD, Susser E, Rotrosen J, Butler PD (2008) Prenatal protein deprivation alters dopamine-mediated behaviors and dopaminergic and glutamatergic receptor binding. Brain Res 1237:62–74PubMedCrossRefGoogle Scholar
  242. Palmer AA, Printz DJ, Butler PD, Dulawa SC, Printz MP (2004) Prenatal protein deprivation in rats induces changes in prepulse inhibition and NMDA receptor binding. Brain Res 996:193–201PubMedCrossRefGoogle Scholar
  243. Papaleo F, Crawley JN, Song J, Lipska BK, Pickel J, Weinberger DR, Chen J (2008) Genetic dissection of the role of catechol-O-methyltransferase in cognition and stress reactivity in mice. J Neurosci 28:8709–8723PubMedCrossRefGoogle Scholar
  244. Peleg-Raibstein D, Knuesel I, Feldon J (2008) Amphetamine sensitization in rats as an animal model of schizophrenia. Behav Brain Res 191:190–201PubMedCrossRefGoogle Scholar
  245. Peleg-Raibstein D, Sydekum E, Feldon J (2006a) Differential effects on prepulse inhibition of withdrawal from two different repeated administration schedules of amphetamine. Int J Neuropsychopharmacol 9:737–749PubMedCrossRefGoogle Scholar
  246. Peleg-Raibstein D, Sydekum E, Russig H, Feldon J (2006b) Withdrawal from continuous amphetamine administration abolishes latent inhibition but leaves prepulse inhibition intact. Psychopharmacology (Berl) 185:226–239CrossRefGoogle Scholar
  247. Peleg-Raibstein D, Sydekum E, Russig H, Feldon J (2006c) Withdrawal from repeated amphetamine administration leads to disruption of prepulse inhibition but not to disruption of latent inhibition. J Neural Transm 113:1323–1336PubMedCrossRefGoogle Scholar
  248. Peleg-Raibstein D, Yee BK, Feldon J, Hauser J (2009) The amphetamine sensitization model of schizophrenia: relevance beyond psychotic symptoms? Psychopharmacology (Berl) 206:603–621CrossRefGoogle Scholar
  249. Penschuck S, Flagstad P, Didriksen M, Leist M, Michael-Titus AT (2006) Decrease in parvalbumin-expressing neurons in the hippocampus and increased phencyclidine-induced locomotor activity in the rat methylazoxymethanol (MAM) model of schizophrenia. Eur J Neurosci 23:279–284PubMedCrossRefGoogle Scholar
  250. Perry W, Minassian A, Paulus MP, Young JW, Kincaid MJ, Ferguson EJ, Henry BL, Zhuang X, Masten VL, Sharp RF, Geyer MA (2009) A reverse-translational study of dysfunctional exploration in psychiatric disorders: from mice to men. Arch Gen Psychiatry 66:1072–1080PubMedCrossRefGoogle Scholar
  251. Phillips KG, Cotel MC, McCarthy AP, Edgar DM, Tricklebank M, O’Neill MJ, Jones MW, Wafford KA (2012) Differential effects of NMDA antagonists on high frequency and gamma EEG oscillations in a neurodevelopmental model of schizophrenia. Neuropharmacology 62:1359–1370PubMedCrossRefGoogle Scholar
  252. Piontkewitz Y, Arad M, Weiner I (2011) Abnormal trajectories of neurodevelopment and behavior following in utero insult in the rat. Biol Psychiatry 70:842–851PubMedCrossRefGoogle Scholar
  253. Piontkewitz Y, Arad M, Weiner I (2012) Tracing the development of psychosis and its prevention: what can be learned from animal models. Neuropharmacology 62:1273–1289PubMedCrossRefGoogle Scholar
  254. Piontkewitz Y, Assaf Y, Weiner I (2009) Clozapine administration in adolescence prevents postpubertal emergence of brain structural pathology in an animal model of schizophrenia. Biol Psychiatry 66:1038–1046PubMedCrossRefGoogle Scholar
  255. Pletnikov MV, Ayhan Y, Nikolskaia O, Xu Y, Ovanesov MV, Huang H, Mori S, Moran TH, Ross CA (2008) Inducible expression of mutant human DISC1 in mice is associated with brain and behavioral abnormalities reminiscent of schizophrenia. Mol Psychiatry 13:173–186PubMedCrossRefGoogle Scholar
  256. Pouzet B, Welzl H, Gubler MK, Broersen L, Veenman CL, Feldon J, Rawlins JN, Yee BK (1999) The effects of NMDA-induced retrohippocampal lesions on performance of four spatial memory tasks known to be sensitive to hippocampal damage in the rat. Eur J Neurosci 11:123–140PubMedCrossRefGoogle Scholar
  257. Powell SB, Young JW, Ong JC, Caron MG, Geyer MA (2008) Atypical antipsychotics clozapine and quetiapine attenuate prepulse inhibition deficits in dopamine transporter knockout mice. Behav Pharmacol 19:562–565PubMedCrossRefGoogle Scholar
  258. Pryce CR, Feldon J (2003) Long-term neurobehavioural impact of the postnatal environment in rats: manipulations, effects and mediating mechanisms. Neurosci Biobehav Rev 27:57–71PubMedCrossRefGoogle Scholar
  259. Pryce CR, Ruedi-Bettschen D, Dettling AC, Feldon J (2002) Early life stress: long-term physiological impact in rodents and primates. News Physiol Sci 17:150–155PubMedGoogle Scholar
  260. Quednow BB, Ettinger U, Mossner R, Rujescu D, Giegling I, Collier DA, Schmechtig A, Kuhn KU, Möller HJ, Maier W, Wagner M, Kumari V (2011) The schizophrenia risk allele C of the TCF4 rs9960767 polymorphism disrupts sensorimotor gating in schizophrenia spectrum and healthy volunteers. J Neurosci 31:6684–6691PubMedCrossRefGoogle Scholar
  261. Quednow BB, Schmechtig A, Ettinger U, Petrovsky N, Collier DA, Vollenweider FX, Wagner M, Kumari V (2009) Sensorimotor gating depends on polymorphisms of the serotonin-2A receptor and catechol-O-methyltransferase, but not on neuregulin-1 Arg38Gln genotype: a replication study. Biol Psychiatry 66:614–620PubMedCrossRefGoogle Scholar
  262. Ranade SC, Rose A, Rao M, Gallego J, Gressens P, Mani S (2008) Different types of nutritional deficiencies affect different domains of spatial memory function checked in a radial arm maze. Neuroscience 152:859–866PubMedCrossRefGoogle Scholar
  263. Rapoport JL, Addington AM, Frangou S, Psych MR (2005) The neurodevelopmental model of schizophrenia: update 2005. Mol Psychiatry 10:434–449PubMedCrossRefGoogle Scholar
  264. Reichenberg A (2005) Cognitive impairment as a risk factor for psychosis. Dialogues Clin Neurosci 7:31–38PubMedGoogle Scholar
  265. Ridley RM (1994) The psychology of perserverative and stereotyped behaviour. Prog Neurobiol 44:221–231PubMedCrossRefGoogle Scholar
  266. Robinson TE, Becker JB (1986) Enduring changes in brain and behavior produced by chronic amphetamine administration: a review and evaluation of animal models of amphetamine psychosis. Brain Res 396:157–198PubMedCrossRefGoogle Scholar
  267. Rojas P, Joodmardi E, Hong Y, Perlmann T, Ogren SO (2007) Adult mice with reduced Nurr1 expression: an animal model for schizophrenia. Mol Psychiatry 12:756–766PubMedCrossRefGoogle Scholar
  268. Romero E, Ali C, Molina-Holgado E, Castellano B, Guaza C, Borrell J (2007) Neurobehavioral and immunological consequences of prenatal immune activation in rats. Influence of antipsychotics. Neuropsychopharmacology 32:1791–1804PubMedCrossRefGoogle Scholar
  269. Romero E, Guaza C, Castellano B, Borrell J (2010) Ontogeny of sensorimotor gating and immune impairment induced by prenatal immune challenge in rats: implications for the etiopathology of schizophrenia. Mol Psychiatry 15:372–383PubMedCrossRefGoogle Scholar
  270. Roussos P, Giakoumaki SG, Adamaki E, Anastasios G, Nikos RK, Bitsios P (2011) The association of schizophrenia risk D-amino acid oxidase polymorphisms with sensorimotor gating, working memory and personality in healthy males. Neuropsychopharmacology 36:1677–1688PubMedCrossRefGoogle Scholar
  271. Rummel-Kluge C, Komossa K, Schwarz S, Hunger H, Schmid F, Kissling W, Davis JM, Leucht S (2012) Second-generation antipsychotic drugs and extrapyramidal side effects: a systematic review and meta-analysis of head-to-head comparisons. Schizophr Bull 38:167–177PubMedCrossRefGoogle Scholar
  272. Russig H, Murphy CA, Feldon J (2002) Clozapine and haloperidol reinstate latent inhibition following its disruption during amphetamine withdrawal. Neuropsychopharmacology 26:765–777PubMedCrossRefGoogle Scholar
  273. Russig H, Murphy CA, Feldon J (2005) Behavioural consequences of withdrawal from three different administration schedules of amphetamine. Behav Brain Res 165:26–35PubMedCrossRefGoogle Scholar
  274. Sams-Dodd F (1995) Distinct effects of d-amphetamine and phencyclidine on the social behaviour of rats. Behav Pharmacol 6:55–65PubMedGoogle Scholar
  275. Sams-Dodd F (1996) Phencyclidine-induced stereotyped behaviour and social isolation in rats: a possible animal model of schizophrenia. Behav Pharmacol 7:3–23PubMedGoogle Scholar
  276. Sams-Dodd F (1999) Phencyclidine in the social interaction test: an animal model of schizophrenia with face and predictive validity. Rev Neurosci 10:59–90PubMedCrossRefGoogle Scholar
  277. Sams-Dodd F, Lipska BK, Weinberger DR (1997) Neonatal lesions of the rat ventral hippocampus result in hyperlocomotion and deficits in social behaviour in adulthood. Psychopharmacology (Berl) 132:303–310CrossRefGoogle Scholar
  278. Sanders AR, Duan J, Levinson DF, Shi J, He D, Hou C, Burrell GJ, Rice JP, Nertney DA, Olincy A, Rozic P, Vinogradov S, Buccola NG, Mowry BJ, Freedman R, Amin F, Black DW, Silverman JM, Byerley WF, Crowe RR, Cloninger CR, Martinez M, Gejman PV (2008) No significant association of 14 candidate genes with schizophrenia in a large European ancestry sample: implications for psychiatric genetics. Am J Psychiatry 165:497–506PubMedCrossRefGoogle Scholar
  279. Schiller D, Zuckerman L, Weiner I (2006) Abnormally persistent latent inhibition induced by lesions to the nucleus accumbens core, basolateral amygdala and orbitofrontal cortex is reversed by clozapine but not by haloperidol. J Psychiatr Res 40:167–177PubMedCrossRefGoogle Scholar
  280. Schmadel S, Schwabe K, Koch M (2004) Effects of neonatal excitotoxic lesions of the entorhinal cortex on cognitive functions in the adult rat. Neuroscience 128:365–374PubMedCrossRefGoogle Scholar
  281. Schneider M, Koch M (2005) Deficient social and play behavior in juvenile and adult rats after neonatal cortical lesion: effects of chronic pubertal cannabinoid treatment. Neuropsychopharmacology 30:944–957PubMedCrossRefGoogle Scholar
  282. Schwabe K, Enkel T, Klein S, Schutte M, Koch M (2004) Effects of neonatal lesions of the medial prefrontal cortex on adult rat behaviour. Behav Brain Res 153:21–34PubMedCrossRefGoogle Scholar
  283. Schwabe K, Klein S, Koch M (2006) Behavioural effects of neonatal lesions of the medial prefrontal cortex and subchronic pubertal treatment with phencyclidine of adult rats. Behav Brain Res 168:150–160PubMedCrossRefGoogle Scholar
  284. Seeman P (1987) Dopamine receptors and the dopamine hypothesis of schizophrenia. Synapse 1:133–152PubMedCrossRefGoogle Scholar
  285. Seillier A, Giuffrida A (2009) Evaluation of NMDA receptor models of schizophrenia: divergences in the behavioral effects of sub-chronic PCP and MK-801. Behav Brain Res 204:410–415PubMedCrossRefGoogle Scholar
  286. Selten JP, van der Graaf Y, van Duursen R, Gispen-de Wied CC, Kahn RS (1999) Psychotic illness after prenatal exposure to the 1953 Dutch Flood Disaster. Schizophr Res 35:243–245PubMedCrossRefGoogle Scholar
  287. Shalev U, Weiner I (2001) Gender-dependent differences in latent inhibition following prenatal stress and corticosterone administration. Behav Brain Res 126:57–63PubMedCrossRefGoogle Scholar
  288. Shenton ME, Dickey CC, Frumin M, McCarley RW (2001) A review of MRI findings in schizophrenia. Schizophr Res 49:1–52PubMedCrossRefGoogle Scholar
  289. Shi L, Fatemi SH, Sidwell RW, Patterson PH (2003) Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring. J Neurosci 23:297–302PubMedGoogle Scholar
  290. Shoemaker JM, Pitcher L, Noh HR, Swerdlow NR (2003) Quetiapine produces a prolonged reversal of the sensorimotor gating-disruptive effects of basolateral amygdala lesions in rats. Behav Neurosci 117:136–143PubMedCrossRefGoogle Scholar
  291. Simen AA, DiLeone R, Arnsten AF (2009) Primate models of schizophrenia: future possibilities. Prog Brain Res 179:117–125PubMedCrossRefGoogle Scholar
  292. Sircar R (2003) Postnatal phencyclidine-induced deficit in adult water maze performance is associated with N-methyl-D-aspartate receptor upregulation. Int J Dev Neurosci 21:159–167PubMedCrossRefGoogle Scholar
  293. Smith SE, Li J, Garbett K, Mirnics K, Patterson PH (2007) Maternal immune activation alters fetal brain development through interleukin-6. J Neurosci 27:10695–10702PubMedCrossRefGoogle Scholar
  294. Spielewoy C, Biala G, Roubert C, Hamon M, Betancur C, Giros B (2001) Hypolocomotor effects of acute and daily d-amphetamine in mice lacking the dopamine transporter. Psychopharmacology (Berl) 159:2–9CrossRefGoogle Scholar
  295. Stefani MR, Moghaddam B (2005) Transient N-methyl-D-aspartate receptor blockade in early development causes lasting cognitive deficits relevant to schizophrenia. Biol Psychiatry 57:433–436PubMedCrossRefGoogle Scholar
  296. Steinpreis RE (1996) The behavioral and neurochemical effects of phencyclidine in humans and animals: some implications for modeling psychosis. Behav Brain Res 74:45–55PubMedCrossRefGoogle Scholar
  297. Sullivan PF (2005) The genetics of schizophrenia. PLoS Med 2:e212PubMedCrossRefGoogle Scholar
  298. Swerdlow NR, Braff DL, Geyer MA, Koob GF (1986) Central dopamine hyperactivity in rats mimics abnormal acoustic startle response in schizophrenics. Biol Psychiatry 21:23–33PubMedCrossRefGoogle Scholar
  299. Swerdlow NR, Geyer MA (1998) Using an animal model of deficient sensorimotor gating to study the pathophysiology and new treatments of schizophrenia. Schizophr Bull 24:285–301PubMedCrossRefGoogle Scholar
  300. Swerdlow NR, Weber M, Qu Y, Light GA, Braff DL (2008) Realistic expectations of prepulse inhibition in translational models for schizophrenia research. Psychopharmacology (Berl) 199:331–388CrossRefGoogle Scholar
  301. Tandon R, Nasrallah HA, Keshavan MS (2009) Schizophrenia, “just the facts” 4. Clinical features and conceptualization. Schizophr Res 110:1–23PubMedCrossRefGoogle Scholar
  302. Tandon R, Nasrallah HA, Keshavan MS (2010) Schizophrenia, “just the facts” 5. Treatment and prevention. Past, present, and future. Schizophr Res 122:1–23PubMedCrossRefGoogle Scholar
  303. Tarantino LM, Bucan M (2000) Dissection of behavior and psychiatric disorders using the mouse as a model. Hum Mol Genet 9:953–965PubMedCrossRefGoogle Scholar
  304. Tenn CC, Fletcher PJ, Kapur S (2005a) A putative animal model of the “prodromal” state of schizophrenia. Biol Psychiatry 57:586–593PubMedCrossRefGoogle Scholar
  305. Tenn CC, Kapur S, Fletcher PJ (2005b) Sensitization to amphetamine, but not phencyclidine, disrupts prepulse inhibition and latent inhibition. Psychopharmacology (Berl) 180:366–376CrossRefGoogle Scholar
  306. Tonkiss J, Almeida SS, Galler JR (1998) Prenatally malnourished female but not male rats show increased sensitivity to MK-801 in a differential reinforcement of low rates task. Behav Pharmacol 9:49–60PubMedGoogle Scholar
  307. Treadway MT, Zald DH (2011) Reconsidering anhedonia in depression: lessons from translational neuroscience. Neurosci Biobehav Rev 35:537–555PubMedCrossRefGoogle Scholar
  308. Tueting P, Doueiri MS, Guidotti A, Davis JM, Costa E (2006) Reelin down-regulation in mice and psychosis endophenotypes. Neurosci Biobehav Rev 30:1065–1077PubMedCrossRefGoogle Scholar
  309. Uehara T, Sumiyoshi T, Seo T, Itoh H, Matsuoka T, Suzuki M, Kurachi M (2009) Long-term effects of neonatal MK-801 treatment on prepulse inhibition in young adult rats. Psychopharmacology (Berl) 206:623–630CrossRefGoogle Scholar
  310. Vaillancourt C, Boksa P (1998) Caesarean section birth with general anesthesia increases dopamine-mediated behavior in the adult rat. Neuroreport 9:2953–2959PubMedCrossRefGoogle Scholar
  311. van den Buuse M (2010) Modeling the positive symptoms of schizophrenia in genetically modified mice: pharmacology and methodology aspects. Schizophr Bull 36:246–270PubMedCrossRefGoogle Scholar
  312. van der Staay FJ, Arndt SS, Nordquist RE (2009) Evaluation of animal models of neurobehavioral disorders. Behav Brain Funct 5:11PubMedCrossRefGoogle Scholar
  313. van Os J, Selten JP (1998) Prenatal exposure to maternal stress and subsequent schizophrenia. The, May 1940 invasion of The Netherlands. Br J Psychiatry 172:324–326PubMedCrossRefGoogle Scholar
  314. Vanover KE, Weiner DM, Makhay M, Veinbergs I, Gardell LR, Lameh J, Del Tredici AL, Piu F, Schiffer HH, Ott TR, Burstein ES, Uldam AK, Thygesen MB, Schlienger N, Andersson CM, Son TY, Harvey SC, Powell SB, Geyer MA, Tolf BR, Brann MR, Davis RE (2006) Pharmacological and behavioral profile of N-(4-fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)-N’-(4-(2-methylpropyloxy)phen ylmethyl) carbamide (2R,3R)-dihydroxybutanedioate (2:1) (ACP-103), a novel 5-hydroxytryptamine(2A) receptor inverse agonist. J Pharmacol Exp Ther 317:910–918PubMedCrossRefGoogle Scholar
  315. Venerosi A, Valanzano A, Cirulli F, Alleva E, Calamandrei G (2004) Acute global anoxia during C-section birth affects dopamine-mediated behavioural responses and reactivity to stress. Behav Brain Res 154:155–164PubMedCrossRefGoogle Scholar
  316. Vollenweider FX, Kometer M (2010) The neurobiology of psychedelic drugs: implications for the treatment of mood disorders. Nat Rev Neurosci 11:642–651PubMedCrossRefGoogle Scholar
  317. Vuillermot S, Feldon J, Meyer U (2011) Nurr1 is not essential for the development of prepulse inhibition deficits induced by prenatal immune activation. Brain Behav Immun 25:1316–1321PubMedCrossRefGoogle Scholar
  318. Vuillermot S, Weber L, Feldon J, Meyer U (2010) A longitudinal examination of the neurodevelopmental impact of prenatal immune activation in mice reveals primary defects in dopaminergic development relevant to schizophrenia. J Neurosci 30:1270–1287PubMedCrossRefGoogle Scholar
  319. Wang CZ, Johnson KM (2007) The role of caspase-3 activation in phencyclidine-induced neuronal death in postnatal rats. Neuropsychopharmacology 32:1178–1194PubMedCrossRefGoogle Scholar
  320. Warburton EC, Joseph MH, Feldon J, Weiner I, Gray JA (1994) Antagonism of amphetamine-induced disruption of latent inhibition in rats by haloperidol and ondansetron: implications for a possible antipsychotic action of ondansetron. Psychopharmacology (Berl) 114:657–664CrossRefGoogle Scholar
  321. Wedzony K, Fijal K, Mackowiak M, Chocyk A (2008a) Detrimental effect of postnatal blockade of N-methyl-D-aspartate receptors on sensorimotor gating is reversed by neuroleptic drugs. Pharmacol Rep 60:856–864PubMedGoogle Scholar
  322. Wedzony K, Fijal K, Mackowiak M, Chocyk A, Zajaczkowski W (2008b) Impact of postnatal blockade of N-methyl-D-aspartate receptors on rat behavior: a search for a new developmental model of schizophrenia. Neuroscience 153:1370–1379PubMedCrossRefGoogle Scholar
  323. Weinberger DR (1987) Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry 44:660–669PubMedCrossRefGoogle Scholar
  324. Weinberger DR, Egan MF, Bertolino A, Callicott JH, Mattay VS, Lipska BK, Berman KF, Goldberg TE (2001) Prefrontal neurons and the genetics of schizophrenia. Biol Psychiatry 50:825–844PubMedCrossRefGoogle Scholar
  325. Weinberger DR, Lipska BK (1995) Cortical maldevelopment, anti-psychotic drugs, and schizophrenia: a search for common ground. Schizophr Res 16:87–110PubMedCrossRefGoogle Scholar
  326. Weiner I (2003) The “two-headed” latent inhibition model of schizophrenia: modeling positive and negative symptoms and their treatment. Psychopharmacology (Berl) 169:257–297CrossRefGoogle Scholar
  327. Weiner I, Arad M (2009) Using the pharmacology of latent inhibition to model domains of pathology in schizophrenia and their treatment. Behav Brain Res 204:369–386PubMedCrossRefGoogle Scholar
  328. Weiner I, Bernasconi E, Broersen LM, Feldon J (1997a) Amphetamine-induced disruption of latent inhibition depends on the nature of the stimulus. Behav Pharmacol 8:442–457PubMedCrossRefGoogle Scholar
  329. Weiner I, Feldon J (1997) The switching model of latent inhibition: an update of neural substrates. Behav Brain Res 88:11–25PubMedCrossRefGoogle Scholar
  330. Weiner I, Gal G, Rawlins JN, Feldon J (1996) Differential involvement of the shell and core subterritories of the nucleus accumbens in latent inhibition and amphetamine-induced activity. Behav Brain Res 81:123–133PubMedCrossRefGoogle Scholar
  331. Weiner I, Tarrasch R, Bernasconi E, Broersen LM, Ruttimann TC, Feldon J (1997b) Amphetamine-induced disruption of latent inhibition is not reinforcer-mediated. Pharmacol Biochem Behav 56:817–826PubMedCrossRefGoogle Scholar
  332. Weiss IC, Feldon J (2001) Environmental animal models for sensorimotor gating deficiencies in schizophrenia: a review. Psychopharmacology (Berl) 156:305–326CrossRefGoogle Scholar
  333. Willner P (1984) The validity of animal models of depression. Psychopharmacology (Berl) 83:1–16CrossRefGoogle Scholar
  334. Willner P (1986) Validation criteria for animal models of human mental disorders: learned helplessness as a paradigm case. Prog Neuropsychopharmacol Biol Psychiatry 10:677–690PubMedCrossRefGoogle Scholar
  335. Wolff AR, Bilkey DK (2008) Immune activation during mid-gestation disrupts sensorimotor gating in rat offspring. Behav Brain Res 190:156–159PubMedCrossRefGoogle Scholar
  336. Wood SJ, Pantelis C, Velakoulis D, Yucel M, Fornito A, McGorry PD (2008) Progressive changes in the development toward schizophrenia: studies in subjects at increased symptomatic risk. Schizophr Bull 34:322–329PubMedCrossRefGoogle Scholar
  337. Yee BK (2000) Cytotoxic lesion of the medial prefrontal cortex abolishes the partial reinforcement extinction effect, attenuates prepulse inhibition of the acoustic startle reflex and induces transient hyperlocomotion, while sparing spontaneous object recognition memory in the rat. Neuroscience 95:675–689PubMedCrossRefGoogle Scholar
  338. Yee BK, Feldon J (2009) Distinct forms of prepulse inhibition disruption distinguishable by the associated changes in prepulse-elicited reaction. Behav Brain Res 204:387–395PubMedCrossRefGoogle Scholar
  339. Yee BK, Feldon J, Rawlins JN (1995) Potentiation of amphetamine-induced locomotor activity following NMDA-induced retrohippocampal neuronal loss in the rat. Exp Brain Res 106:356–364PubMedCrossRefGoogle Scholar
  340. Yee BK, Hauser J, Dolgov VV, Keist R, Mohler H, Rudolph U, Feldon J (2004) GABA receptors containing the alpha5 subunit mediate the trace effect in aversive and appetitive conditioning and extinction of conditioned fear. Eur J Neurosci 20:1928–1936PubMedCrossRefGoogle Scholar
  341. Yee BK, Rawlins JN (1998) A comparison between the effects of medial septal lesions and entorhinal cortex lesions on performance of nonspatial working memory tasks and reversal learning. Behav Brain Res 94:281–300PubMedCrossRefGoogle Scholar
  342. Yogev H, Hadar U, Gutman Y, Sirota P (2003) Perseveration and over-switching in schizophrenia. Schizophr Res 61:315–321PubMedCrossRefGoogle Scholar
  343. Young JW, Powell SB, Risbrough V, Marston HM, Geyer MA (2009) Using the MATRICS to guide development of a preclinical cognitive test battery for research in schizophrenia. Pharmacol Ther 122:150–202PubMedCrossRefGoogle Scholar
  344. Zuckerman L, Rehavi M, Nachman R, Weiner I (2003a) Immune activation during pregnancy in rats leads to a postpubertal emergence of disrupted latent inhibition, dopaminergic hyperfunction, and altered limbic morphology in the offspring: a novel neurodevelopmental model of schizophrenia. Neuropsychopharmacology 28:1778–1789PubMedCrossRefGoogle Scholar
  345. Zuckerman L, Rimmerman N, Weiner I (2003b) Latent inhibition in 35-day-old rats is not an “adult” latent inhibition: implications for neurodevelopmental models of schizophrenia. Psychopharmacology (Berl) 169:298–307CrossRefGoogle Scholar
  346. Zuckerman L, Weiner I (2005) Maternal immune activation leads to behavioral and pharmacological changes in the adult offspring. J Psychiatr Res 39:311–323PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Daria Peleg-Raibstein
    • 1
  • Joram Feldon
    • 2
    Email author
  • Urs Meyer
    • 3
  1. 1.Laboratory of Translational Nutrition BiologySwiss Federal Institute of Technology (ETH) ZürichSchwerzenbachSwitzerland
  2. 2.The Max Stern Academic College of Emek YezreelEmek YezreelIsrael
  3. 3.Physiology and Behaviour LaboratorySwiss Federal Institute of Technology (ETH) ZürichSchwerzenbachSwitzerland

Personalised recommendations