Advertisement

Experimental Brain Research

, Volume 173, Issue 2, pp 243–257 | Cite as

Prenatal and postnatal maternal contributions in the infection model of schizophrenia

  • Urs Meyer
  • Severin Schwendener
  • Joram Feldon
  • Benjamin K. YeeEmail author
Research Article

Abstract

Epidemiological studies have indicated that the risk of schizophrenia is enhanced by prenatal maternal infection with viral or bacterial pathogens. Recent experimentation in rodents has yielded additional support for a causal relationship between prenatal immune challenge and the emergence of psychosis-related abnormalities in brain and behaviour in later life. However, little is known about the putative roles of maternal postnatal factors in triggering and modulating the emergence of psychopathology following prenatal immunological stimulation. Here, we aimed to dissect the relative contributions of prenatal inflammatory events and postnatal maternal factors in precipitating juvenile and adult psychopathology in the resulting offspring with a cross-fostering design. Pregnant mice were exposed to the viral mimic, polyriboinosinic-polyribocytidilic acid (PolyI:C; at 5 mg/kg, intravenously), or vehicle treatment on gestation day 9, and offspring born to PolyI:C- and vehicle-treated dams were then simultaneously cross-fostered to surrogate rearing mothers, which had either experienced inflammatory or vehicle treatment during pregnancy. Prenatal PolyI:C administration did not affect the expression of latent inhibition (LI) at a juvenile stage of development, but led to the post-pubertal emergence of LI disruption in both aversive classical and instrumental conditioning regardless of the postnatal rearing condition. In addition, deficits in conditioning as such led to a pre- and post-pubertal loss of LI in prenatal control animals that were adopted by PolyI:C-treated surrogate mothers. Our findings thus indicate that the adoption of prenatally immune-challenged neonates by control surrogate mothers does not possess any protective effects against the subsequent emergence of psychopathology in adulthood. At the same time, however, the present study highlights for the first time that the adoption of prenatal control animals by immune-challenged rearing mothers is sufficient to precipitate learning disabilities in the juvenile and adult offspring.

Keywords

Adoption Animal model Cytokines Infection Latent inhibition Learning PolyI:C Schizophrenia 

Notes

Acknowledgements

The present study was supported by the Swiss Federal Institute of Technology Zurich, with additional support from the National Centre for Competence in Research: Neural Plasticity and Repair, Swiss National Science Foundation. We are extremely grateful to Peter Schmid for his technical assistance. We also remain indebted to Jeanne Michel and Pascal Guela for their care of the animals, and to Dr. Frank Bootz for his veterinary expertise.

References

  1. Andersen SL, LeBlanc CJ, Lyss PJ (2001) Maturational increases in c-fos expression in the ascending dopamine systems. Synapse 41:345–350PubMedCrossRefGoogle Scholar
  2. Ashdown H, Dumont Y, Ng M, Poole S, Boksa P, Luheshi GN (2006) The role of cytokines in mediating effects of prenatal infection on the fetus: implications for schizophrenia. Mol Psychiatry 11:47–55PubMedCrossRefGoogle Scholar
  3. Bolanos CA, Glatt SJ, Jackson D (1998) Subsensitivity to dopaminergic drugs in periadolescent rats: a behavioral and neurochemical analysis. Brain Res Dev Brain Res 111:25–33PubMedCrossRefGoogle Scholar
  4. Borrell J, Vela JM, Arévalo-Martin A, Molina-Holgado E, Guaza C (2002) Prenatal immune challenge disrupts sensorimotor gating in adult rats: implications for the etiopathogenesis of schizophrenia. Neuropsychopharmacology 26:204–221PubMedCrossRefGoogle Scholar
  5. Bracha HS, Torrey EF, Bigelow LB, Lohr JB, Linington BB (1991) Subtle signs of prenatal maldevelopment of the hand ectoderm in schizophrenia: a preliminary monozygotic twin study. Biol Psychiatry 30:719–725PubMedCrossRefGoogle Scholar
  6. Bracha HS, Torrey EF, Gottesman II, Bigelow LB, Cunniff C (1992) Second-trimester markers of fetal size in schizophrenia: a study of monozygotic twins. Am J Psychiatry 149:1355–1361PubMedGoogle Scholar
  7. Brake WG, Zhang TY, Diorio J, Meaney MJ, Gratton A (2004) Influence of early postnatal rearing conditions on mesocorticolimbic dopamine and behavioural responses to psychostimulants and stressors in adult rats. Eur J Neurosci 19:1863–1874PubMedCrossRefGoogle Scholar
  8. Brayden RM, Altemeier WA, Tucker DD, Dietrich MS, Vietze P (1992) Antecedents of child neglect in the first two years of life. J Pediatr 120:426–429PubMedCrossRefGoogle Scholar
  9. Brown AS, Schaefer CA, Wyatt RJ, Goetz R, Begg MD, Gorman JM, Susser ES (2000) Maternal exposure to respiratory infections and adult schizophrenia spectrum disorders: a prospective birth cohort study. Schizophr Bull 26:287–295PubMedGoogle Scholar
  10. Brown AS, Begg MD, Gravenstein S, Schaefer CA, Wyatt RJ, Bresnahan M, Babulas VP, Susser ES (2004a) Serologic evidence of prenatal influenza in the etiology of schizophrenia. Arch Gen Psychiatry 61:774–780CrossRefGoogle Scholar
  11. Brown AS, Hooton J, Schaefer CA, Zhang H, Petkova E, Babulas V, Perrin M, Gorman JM, Susser ES (2004b) Elevated maternal interleukin-8 levels and risk of schizophrenia in adult offspring. Am J Psychiatry 161:889–895CrossRefGoogle Scholar
  12. Buhusi CV, Gray JA, Schmajuk NA (1998) Perplexing effects of hippocampal lesions on latent inhibition: a neural network solution. Behav Neurosci 112:316–351PubMedCrossRefGoogle Scholar
  13. Buka SL, Tsuang MT, Torrey EF, Klebanoff MA, Wagner RL, Yolken RH (2001) Maternal cytokine levels during pregnancy and adult psychosis. Brain Behav Immun 15:411–420PubMedCrossRefGoogle Scholar
  14. Cardno AG, Marshall EJ, Coid B, Macdonald AM, Ribchester TR, Davies NJ, Venturi P, Jones LA, Lewis SW, Sham PC, Gottesman II, Farmer AE, McGuffin P, Reveley AM, Murray RM (1999) Heritability estimates for psychotic disorders: the Maudsley twin psychosis series. Arch Gen Psychiatry 56:162–168PubMedCrossRefGoogle Scholar
  15. 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
  16. Ellenbroek BA, Cools AR (2002) Early maternal deprivation and prepulse inhibition: the role of the postdeprivation environment. Pharmacol Biochem Behav 73:177–184PubMedCrossRefGoogle Scholar
  17. Fatemi SH, Emamian ES, Kist D, Sidwell RW, Nakajima K, Akhter P, Shier A, Sheikh S, Bailey K (1999) Defective corticogenesis and reduction in Reelin immunoreactivity in cortex and hippocampus of prenatally infected neonatal mice. Mol Psychiatry 4:145–154PubMedCrossRefGoogle Scholar
  18. Fatemi SH, Earle J, Kanodia R, Kist D, Emamian ES, Patterson PH, Shi L, Sidwell R (2002) Prenatal viral infection leads to pyramidal cell atrophy and macrocephaly in adulthood: implications for genesis of autism and schizophrenia. Cell Mol Neurobiol 22:25–33PubMedCrossRefGoogle Scholar
  19. Fatemi SH, Pearce DA, Brooks AI, Sidwell RW (2005) Prenatal viral infection in mouse causes differential expression of genes in brains of mouse progeny: a potential animal model for schizophrenia and autism. Synapse 57:91–99PubMedCrossRefGoogle Scholar
  20. 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
  21. Fleming AS, O’Day DH, Kraemer GW (1999) Neurobiology of mother-infant interactions: experience and central nervous system plasticity across development and generations. Neurosci Biobehav Rev 23:673–685PubMedCrossRefGoogle Scholar
  22. 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
  23. Franzek E, Beckmann H (1996) Gene-environment interaction in schizophrenia: season-of-birth effect reveals etiologically different subgroups. Psychopathology 29:14–26PubMedCrossRefGoogle Scholar
  24. Frith CD (1979) Consciousness, information processing and schizophrenia. Br J Psychiatry 134: 225–235PubMedCrossRefGoogle Scholar
  25. Gallo M, Candido A (1995) Dorsal hippocampal lesions impair blocking but not latent inhibition of taste aversion learning in rats. Behav Neurosci 109:413–425PubMedCrossRefGoogle Scholar
  26. Gilmore JH, Jarskog LF (1997) Exposure to infection and brain development: cytokines in the pathogenesis of schizophrenia. Schizophr Res 24:365–367PubMedCrossRefGoogle Scholar
  27. Gilmore JH, Perkins DO, Kliewer MA, Hage ML, Silva SG, Chescheir NC, Hertzberg BS, Sears CA (1996) Fetal brain development of twins assessed in utero by ultrasound: implications for schizophrenia. Schizophr Res 19:141–149PubMedCrossRefGoogle Scholar
  28. Gilmore JH, Jarskog LF, Vadlamudi S, Lauder JM (2004) Prenatal infection and risk for schizophrenia: IL-1beta, IL-6, and TNFalpha inhibit cortical neuron dendrite development. Neuropsychopharmacology 29:1221–1229CrossRefPubMedGoogle Scholar
  29. Gilmore JH, Jarskog LF, Vadlamudi S (2005) Maternal poly I:C exposure during pregnancy regulates TNFalpha, BDNF, and NGF expression in neonatal brain and the maternal-fetal unit of the rat. J Neuroimmunol 159:106–112PubMedCrossRefGoogle Scholar
  30. Goebel MU, Baase J, Pithan V, Exton M, Saller B, Schedlowski M, Limmroth V (2002) Acute interferon beta-1b administration alters hypothalamic-pituitary-adrenal axis activity, plasma cytokines and leukocyte distribution in healthy subjects. Psychoneuroendocrinology 27:881–892PubMedCrossRefGoogle Scholar
  31. 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
  32. Gray JA (1998) Integrating schizophrenia. Schizophr Bull 24:249–266PubMedGoogle Scholar
  33. Gray JA, Feldon J, Rawlins JNP, Hemsley DR, Smith AD (1991) The neuropsychology of schizophrenia. Behav Brain Sci 14:1–84Google Scholar
  34. Haddad JJ, Saade NE, Safieh-Garabedian B (2002) Cytokines and neuro-immune-endocrine interactions: a role for the hypothalamic-pituitary-adrenal revolving axis. J Neuroimmunol 133:1–19PubMedCrossRefGoogle Scholar
  35. Harrison PJ, Weinberger DR (2005) Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol Psychiatry 10:40–68PubMedCrossRefGoogle Scholar
  36. Hemsley DR (1976) Attention and information processing in schizophrenia. Br J Soc Clin Psychol 15:199–209PubMedGoogle Scholar
  37. Hultman CM, Sparen P, Takei N, Murray RM, Cnattingius S (1999) Prenatal and perinatal risk factors for schizophrenia, affective psychosis and reactive psychosis. Br J Med 310:421–425Google Scholar
  38. Infurna RN, Spear LP (1979) Developmental changes in amphetamine-induced taste aversions. Pharmacol Biochem Behav 11:31–35PubMedCrossRefGoogle Scholar
  39. Jakob H, Beckman H (1986) Prenatal development disturbances in the limbic allocortex in schizophrenia. J Neural Transm 65:303–326PubMedCrossRefGoogle Scholar
  40. Kendler KS, Gardner CO, Prescott CA (2002) Toward a comprehensive developmental model for major depression in women. Am J Psychiatry 159:1133–1145PubMedCrossRefGoogle Scholar
  41. Kendler KS, Gardner CO, Prescott CA (2006) Toward a comprehensive developmental model for major depression in men. Am J Psychiatry 163:115–124PubMedCrossRefGoogle Scholar
  42. Leckman JF, Herman AE (2002) Maternal behavior and developmental psychopathology. Biol Psychiatry 51:27–43PubMedCrossRefGoogle Scholar
  43. Lehmann J, Feldon J (2000) Long-term biobehavioral effects of maternal separation in the rat: consistent or confusing? Rev Neurosci 11:383–408PubMedGoogle Scholar
  44. Mäki P, Veijola J, Jones PB, Murray GK, Koponen H, Tienari P, Miettunen J, Tanskanen P, Wahlberg KE, Koskinen J, Lauronen E, Isohanni M (2005) Predictors of schizophrenia—a review. Br Med Bull 73:1–15PubMedCrossRefGoogle Scholar
  45. Maughan B, McCarthy G (1997) Childhood adversities and psychosocial disorders. Br Med Bull 53:156–169PubMedGoogle Scholar
  46. Mednick SA, Machon RA, Huttunen MO, Bonett D (1988) Adult schizophrenia following prenatal exposure to an influenza epidemic. Arch Gen Psychiatry 45:189–192PubMedGoogle Scholar
  47. Meek LR, Dittel PL, Sheehan MC, Chan JY, Kjolhaug SR (2001) Effects of stress during pregnancy on maternal behavior in mice. Physiol Behav 72:473–479PubMedCrossRefGoogle Scholar
  48. Meyer U, Chang de LT, Feldon J, Yee BK (2004) Expression of the CS- and US-pre-exposure effects in the conditioned taste aversion paradigm and their abolition following systemic amphetamine treatment in C57BL6/J mice. Neuropsychopharmacology 29:2140–2148PubMedCrossRefGoogle Scholar
  49. 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
  50. Meyer U, Feldon J, Schedlowski M, Yee BK (2006) Immunological stress at the maternal-foetal interface: a link between neurodevelopment and adult psychopathology. Brain Behav Immun (in press)Google Scholar
  51. Moser PC, Hitchcock JM, Lister S, Moran PM (2000) The pharmacology of latent inhibition as an animal model of schizophrenia. Brain Res Rev 33:275–307CrossRefPubMedGoogle Scholar
  52. Murray RM, Jones P, O’Callaghan E (1991) Fetal brain development and later schizophrenia. Ciba Found Symp 156:155–163PubMedGoogle Scholar
  53. Nuechterlein KH, Dawson ME (1984) Information processing and attentional functioning in the developmental course of schizophrenic disorders. Schizophr Bull 10:160–203PubMedGoogle Scholar
  54. O’Callaghan E, Sham PC, Takei N, Murray G, Glover G, Hare EH, Murray RM (1994) The relationship of schizophrenic births to 16 infectious diseases. Br J Psychiatry 165:353–356PubMedCrossRefGoogle Scholar
  55. 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 response, habituation and latent inhibition. Eur J Neurosci 15:1983–1990PubMedCrossRefGoogle Scholar
  56. 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
  57. Parker G, Hadzi-Pavlovic D, Greenwald S, Weissman M (1995) Low parental care as a risk factor to lifetime depression in a community sample. J Affect Disord 33:173–180PubMedCrossRefGoogle Scholar
  58. Patin V, Lordi B, Vincent A, Thoumas JL, Vaudry H, Caston J (2002) Effects of prenatal stress on maternal behavior in the rat. Brain Res Dev Brain Res 139:1–8PubMedCrossRefGoogle Scholar
  59. Patterson PH (2002) Maternal infection: window on neuroimmune interactions in fetal brain development and mental illness. Curr Opin Neurobiol 12:115–118PubMedCrossRefGoogle Scholar
  60. Pearce BD (2001) Schizophrenia and viral infection during neurodevelopment: a focus on mechanisms. Mol Psychiatry 6:634–646PubMedCrossRefGoogle Scholar
  61. Perry W, Braff DL (1994) Information-processing deficits and thought disorder in schizophrenia. Am J Psychiatry 151:363–367PubMedGoogle Scholar
  62. Petronis A (2004) The origin of schizophrenia: genetic thesis, epigenetic antithesis, and resolving synthesis. Biol Psychiatry 55:965–970PubMedCrossRefGoogle Scholar
  63. Pothuizen HH, Jongen-Relo AL, Feldon J, Yee BK (2006) Latent inhibition of conditioned taste aversion is not disrupted, but can be enhanced, by selective nucleus accumbens shell lesions in rats. Neuroscience 137:1119–1130PubMedCrossRefGoogle Scholar
  64. 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
  65. Pryce CR, Ruedi-Bettschen D, Dettling AC, Weston A, Russig H, Ferger B, Feldon J (2005) Long-term effects of early-life environmental manipulations in rodents and primates: potential animal models in depression research. Neurosci Biobehav Rev 29:649–674PubMedCrossRefGoogle Scholar
  66. Purves D, Bonardi C, Hall G (1995) Enhancement of latent inhibition in rats with electrolytic lesions of the hippocampus. Behav Neurosci 109:366–370PubMedCrossRefGoogle Scholar
  67. Rapoport JL, Addington AM, Frangou S, Psych MR (2005) The neurodevelopmental model of schizophrenia: update 2005. Mol Psychiatry 10:434–449PubMedCrossRefGoogle Scholar
  68. Reilly S, Harley C, Revusky S (1993) Ibotenate lesions of the hippocampus enhance latent inhibition in conditioned taste aversion and increase resistance to extinction in conditioned taste preference. Behav Neurosci 107:996–1004PubMedCrossRefGoogle Scholar
  69. Russig H, Kovacevic A, Murphy CA, Feldon J (2003) Haloperidol and clozapine antagonise amphetamine-induced disruption of latent inhibition of conditioned taste aversion. Psychopharmacology 170:263–270PubMedCrossRefGoogle Scholar
  70. Schmajuk N (2005) Brain-behaviour relationships in latent inhibition: a computational model. Neurosci Biobehav Rev 29:1001–1020PubMedCrossRefGoogle Scholar
  71. Schmajuk NA, Christiansen B, Cox L (2000) Haloperidol reinstates latent inhibition impaired by hippocampal lesions: data and theory. Behav Neurosci 114:659–670PubMedCrossRefGoogle Scholar
  72. Schmajuk NA, Cox L, Gray JA (2001) Nucleus accumbens, entorhinal cortex and latent inhibition: a neural network model. Behav Brain Res 118:123–141PubMedCrossRefGoogle Scholar
  73. 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
  74. Silverman MN, Pearce BD, Biron CA, Miller AH (2005) Immune modulation of the hypothalamic-pituitary-adrenal (HPA) axis during viral infection. Viral Immunol 18:41–78PubMedCrossRefGoogle Scholar
  75. Spear LP (2000) The adolescent brain and age-related behavioral manifestations. Neurosci Biobehav Rev 24:417–463PubMedCrossRefGoogle Scholar
  76. Tienari P, Wynne LC, Sorri A, Lahti I, Laksy K, Moring J, Naarala M, Nieminen P, Wahlberg KE (2004) Genotype-environment interaction in schizophrenia-spectrum disorder. Long-term follow-up study of Finnish adoptees. Br J Psychiatry 184:216–222PubMedCrossRefGoogle Scholar
  77. Tsuang M (2000) Schizophrenia: genes and environment. Biol Psychiatry 47:210–220PubMedCrossRefGoogle Scholar
  78. Urakubo A, Jarskog LF, Lieberman JA, Gilmore JH (2001) Prenatal exposure to maternal infection alters cytokine expression in the placenta, amniotic fluid, and fetal brain. Schizophr Res 47:27–36PubMedCrossRefGoogle Scholar
  79. Wahlberg KE, Wynne LC, Oja H, Keskitalo P, Pykalainen L, Lahti I, Moring J, Naarala M, Sorri A, Seitamaa M, Laksy K, Kolassa J, Tienari P (1997) Gene-environment interaction in vulnerability to schizophrenia: findings from the Finnish adoptive family study of schizophrenia. Am J Psychiatry 154:355–362PubMedGoogle Scholar
  80. Walker CD, Deschamps S, Proulx K, Tu M, Salzman C, Woodside B, Lupien S, Gallo-Payet N, Richard D (2004) Mother to infant or infant to mother? Reciprocal regulation of responsiveness to stress in rodents and the implications for humans. J Psychiatry Neurosci 29:364–382PubMedGoogle Scholar
  81. 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 114:657–664PubMedCrossRefGoogle Scholar
  82. Webster JI, Sternberg EM (2004) Role of the hypothalamic-pituitary-adrenal axis, glucocorticoids and glucocorticoid receptors in toxic sequelae of exposure to bacterial and viral products. J Endocrinol 181:207–221PubMedCrossRefGoogle Scholar
  83. Weinberger DR (1987) Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry 44:660–669PubMedGoogle Scholar
  84. Weiner I (2003) The “two-headed” latent inhibition model of schizophrenia: modeling positive and negative symptoms and their treatment. Psychopharmacology 169:257–297PubMedCrossRefGoogle Scholar
  85. Weiner I, Lubow RE, Feldon J (1984) Abolition of the expression but not the acquisition of latent inhibition by chronic amphetamine in rats. Psychopharmacology 83:194–199PubMedCrossRefGoogle Scholar
  86. Weiner I, Lubow RE, Feldon J (1988) Disruption of latent inhibition by acute administration of low doses of amphetamine. Pharmacol Biochem Behav 30:871–888PubMedCrossRefGoogle Scholar
  87. Weiss IC, Feldon J (2001) Environmental animal models for sensorimotor gating deficiencies in schizophrenia: a review. Psychopharmacology 156:305–326PubMedCrossRefGoogle Scholar
  88. Weiss IC, Domeney AM, Heidbreder CA, Moreau JL, Feldon J (2001) Early social isolation, but not maternal separation, affects behavioral sensitization to amphetamine in male and female adult rats. Pharmacol Biochem Behav 70:397–409PubMedCrossRefGoogle Scholar
  89. Zorrilla EP (1997) Multiparous species present problems (and possibilities) to developmentalists. Dev Psychobiol 30:141–150PubMedCrossRefGoogle Scholar
  90. Zuckerman L, Weiner I (2003) Post-pubertal emergence of disrupted latent inhibition following prenatal immune activation. Psychopharmacology 169:308–313PubMedCrossRefGoogle Scholar
  91. 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
  92. 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 28:1778–1789CrossRefGoogle Scholar
  93. 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 169:298–307CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Urs Meyer
    • 1
  • Severin Schwendener
    • 1
  • Joram Feldon
    • 1
  • Benjamin K. Yee
    • 1
    Email author
  1. 1.Laboratory of Behavioural NeurobiologySwiss Federal Institute of Technology ZurichSchwerzenbachSwitzerland

Personalised recommendations