Rat Latent Inhibition and Prepulse Inhibition are Sensitive to Different Manipulations of the Social Environment: A Comprehensive Study of the Environmental Approach to Neurodevelopmental Models of Schizophrenia

  • Joram Feldon
  • Julia Lehmann
  • Christopher Pryce
  • Isabelle Weiss
Part of the Neurobiological Foundation of Aberrant Behaviors book series (NFAB, volume 1)


In the present chapter we review a series of rat studies conducted in our laboratory during the last five years, investigating the long-term consequences of manipulations of the social environment for behavioural processes which are widely recognised as being of direct relevance to psychosis, and in particular to schizophrenia. The ultimate aim of these studies is to ascertain the relevance and robustness of effects induced by manipulations of the rat’s social environment as animal models of important symptoms and features of human psychosis. There are a number of potential advantages to the modelling approach we are taking. Firstly, our research work has been influenced by the evidence that many psychiatric disorders, and notably schizophrenia, emerge out of early developmental aberrations, and the theory that epigenetic changes induced by these early events express themselves later in the life span as clinical disorder (Weinberger, 1987). One approach to the animal modelling of this neurodevelopmental hypothesis of schizophrenia is to perform surgical lesions of specific brain structures in the early postnatal period and to monitor the behavioural consequences of these lesions longterm (Lipska, this volume). Our neurodevelopmental approach and that of some other laboratories is non-surgical, and involves specific manipulation of the social environment which, it is hypothesised, will expose the developing brain to events it is not expecting and/or deprive it of events that it is expecting, leading to long-term change in structure-function of specific brain areas.


Conditioned Stimulus Latent Inhibition Prepulse Inhibition Maternal Separation Acoustic Startle Response 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Denenberg, V.H. (1977) Assessing the effects of early experience. In R.D. Myers, ed. Methods in Psychobiology, Vol III (pp. 127–147 ). New York: Academic Press.Google Scholar
  2. Domeney, A.M. and Feldon, J. (1998) The disruption of prepulse inhibition by social isolation in the Wistar rat: How robust is the effect? Pharmacol Biochem Behav 59: 883–890.PubMedCrossRefGoogle Scholar
  3. Ellenbroek, B.A. and Cools, A.R. (1995) Maternal separation reduces latent inhibition in the conditioned taste aversion paradigm. Neurosci Res Comm, 17: 27–33.Google Scholar
  4. Ellenbroek, B.A. and Cools, A.R. (1998) The neurodevelopment hypothesis of schizophrenia: clinical evidence and animal models. Neurosci Res Comm 22: 127–136.CrossRefGoogle Scholar
  5. Ellenbroek, B.A., van den Kroonenberg, P.T.J.M., Cools, A.R. (1998) The effects of an early stressful life event on sensorimotor gating in adult rats. Schizophrenia Res 30: 251–260.CrossRefGoogle Scholar
  6. Feldon, J., Avnimelech-Gigus, N., Weiner, I. (1990) The effects of pre-and postweaning rearing conditions on latent inhibition and partial reinforcement extinction effect in male rats. Behav Neural Biol 53: 189–204.Google Scholar
  7. Feldon, J., Shalev, U., Weiner, I. (1995) “Super” latent inhibition ( LI) with high dose of amphetamine. Soc Neurosci Abstracts 21: 12–30.Google Scholar
  8. Feldon, J. and Weiner, I. (1988) Long-term attentional deficit in nonhandled males: possible involvement of the dopaminergic system. Psychopharmacol 95: 231–236.Google Scholar
  9. Feldon, J. and Weiner, I. (1992) From an animal model of an attentional deficit towards new insights into the pathophysiology of schizophrenia. J Psychiatry Res 26: 345–366.CrossRefGoogle Scholar
  10. Geyer, M.A., Wilkinson, L.S., Humby, T., Robbins, T.W. (1993) Isolation rearing of rats produces a deficit in prepulse inhibition of acoustic startle similar to that in schizophrenia. Biol Psychiat 34: 361–372.PubMedCrossRefGoogle Scholar
  11. Hall, F.S., Wilkinson, L.S., Humby, T., Robbins, T.W. (1999) Maternal deprivation of neonatal rats produces enduring changes in dopamine function. Synapse 32: 37–43.PubMedCrossRefGoogle Scholar
  12. Jones, G.H., Hernandez, T.D., Kendall, D.A., Marsden, C.A., Robbins, T. W. (1992) Dopaminergic and serotonergic function following isolation rearing in rats: study of behavioural responses and postmortem and in-vivo neurochemistry. Pharmacol Biochem Behav 43: 17–35.PubMedCrossRefGoogle Scholar
  13. Lehmann, J. and Feldon, J. (in press) Long-term bio-behavioural effects of maternal separation in the rat: consistent or confusing? Rev Neurosci.Google Scholar
  14. Lehmann, J., Stöhr, T., Schuller, J., Domeney, A., Heidbreder, C., Feldon, J. (1998) Long-term effects of repeated maternal separation on three different latent inhibition paradigms. Pharmacol Biochem Behav 59: 873–882.PubMedCrossRefGoogle Scholar
  15. Lehmann, L., Pryce, C.R., Bettschen, D., Feldon, J. (1999) The maternal separation paradigm and adult emotionality and cognition in male and female Wistar rats. Pharmacol Biochem Behav 64: 705–715.PubMedCrossRefGoogle Scholar
  16. Lehmann, J., Stöhr, T., Feldon, J. (2000) Long-term effects of prenatal stress experience and postnatal maternal separation on emotionality and attentional processes. Behav Brain Res 107: 133–144.PubMedCrossRefGoogle Scholar
  17. Lehmann, J., Logeay, C., Feldon, J. (in press-a) Long-term effects of a single 24 hour maternal separation on three different latent inhibition paradigms. Psychobiol.Google Scholar
  18. Lehmann, J., Pryce, C.R., Feldon, J. (2000) Lack of effect of an early stressful life event on sensorimotor gating in adult rats. Schizophr Res 41: 365–371.PubMedCrossRefGoogle Scholar
  19. Levine, S. (1960). Stimulation in infancy. Sci Amer 202: 81–86.PubMedCrossRefGoogle Scholar
  20. Liu, D., Diorio, J., Tannenbaum, B., Caldji, C., Francis, D., Freedman, A., Sharma, S., Pearson, D., Plotsky, P. M., and Meaney, M.J. (1997) Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress. Science 277: 1659–1662.PubMedCrossRefGoogle Scholar
  21. Lubow, R.E. (1989) Latent Inhibition and Conditioned Attention Theory. Cambridge, U.K.: CUP.Google Scholar
  22. Lubow, R.E. and Gewirtz, J.C. (1995) Latent inhibition in humans: data, theory, and implications for schizophrenia. Psychol Bull 117: 87–103.PubMedCrossRefGoogle Scholar
  23. Meaney, M.J., Diorio, J., Francis, D., Widdowson, J., LaPlante, P., Caldji, C., Sharma, S., Seckl, J.R., Plotsky, P.M. (1996) Early environmental regulation of forebrain glucocorticoid receptor gene expression: Implications for adrenocortical responses to stress. Dev Neurosci 18: 49–72.PubMedCrossRefGoogle Scholar
  24. Murphy, C.A., Heidbreder, C., Feldon, J. (2000) Cocaine sensitization enhances latent inhibition of a conditioned fear response. Schizophr Res 41: 247 (abstract).CrossRefGoogle Scholar
  25. Robbins, T.W., Jones, G.H., Wilkinson, L.S. (1996) Behavioural and neurochemical effects of early social deprivation in the rat. J Psychopharmacol 10: 39–47.PubMedCrossRefGoogle Scholar
  26. Swerdlow, N.R., Braff, D.L., Taaid, N., Geyer, M.A. (1994) Assessing the validity of an animal model of deficient sensorimotor gating in schizophrenic patients. Arch Gen Psychiatry 51: 139–154.PubMedCrossRefGoogle Scholar
  27. Swerdlow, N.R. and Geyer, M.A. (1998) Using an animal model of deficient sensorimotor gating to study the pathophysiology and new treatments of schizophrenia. Schizophr Bull 24: 285–301.PubMedCrossRefGoogle Scholar
  28. Vollenweider, F.X., Umbricht, D., Geyer, M., Hell, D. (2000) Effects of NMDA-antagonists and 5HT2A-agonists on prepulse inhibition in human volunteers. Schizophr Res 41: 147 (abstract).CrossRefGoogle Scholar
  29. Weinberger, D.R. (1987) Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry 44: 660–669.PubMedCrossRefGoogle Scholar
  30. Weiner, I. and Feldon, J. (1997) The switching model of latent inhibition: an update of neural substrates. Behav Brain Res 88: 11–25.PubMedCrossRefGoogle Scholar
  31. Weiner, I., Feldon, J., Ziv-Harris, D. (1987) Early handling and latent inhibition in the conditioned suppression paradigm. Develop Psychobiol 20: 233–240.CrossRefGoogle Scholar
  32. Weiner, I., Schnabel, I., Lubow, R.E., Feldon, J. (1985) The effects of early handling on latent inhibition in male and female rats. Devel Psychobiol 18: 291–297.CrossRefGoogle Scholar
  33. Weiss, I.C., Feldon, J., Domeney, A. M. (1999). Isolation rearing-induced disruption of prepulse inhibition: further evidence for fragility of the response. Behav Pharmacol 10: 139–149.PubMedCrossRefGoogle Scholar
  34. Weiss, I.C., Domeney, A.M., Feldon, J. (2000) Sex differences in the effects of maternal separation and/or social isolation on sensorimotor gating in adult rats. Schizophr Res 41: 59 (abstract).CrossRefGoogle Scholar
  35. Weiss, I.C., Di lorio, L., Feldon, J., Domeney, A. (2000) Strain differences in the isolation-induced effects on prepulse inhibition of the acoustic startle response and on locomotor activity. Behav Neurosci 114: 364–373.PubMedCrossRefGoogle Scholar
  36. Weiss, I.C., Domeney, A.M., Moreau, J-L., Russig, H., Feldon, J. Dissociation between the effects of pre-weaning and/or post-weaning social isolation on prepulse inhibition and latent inhibition in adult Sprague-Dawley rats. Submitted to Behav Neurosci.Google Scholar
  37. Wilkinson, L.S., Killcross, S.S., Humby, T., Hall, F.S., Geyer, M.A., Robbins, T.W. (1994). Social isolation in the rat produces developmentally specific deficits in prepulse inhibition of the acoustic startle response without disrupting latent inhibition. Neuropsychopharmacol 10: 61–72.Google Scholar
  38. Williams, J.H., Wellman, N.A., Geaney, D.P., Cowen, P.J., Feldon, J., Rawlins, J.N.P. (1998) Reduced latent inhibition in people with schizophrenia: an effect of psychosis or of its treatment. Br J Psychiatry 172: 243–249.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2000

Authors and Affiliations

  • Joram Feldon
  • Julia Lehmann
  • Christopher Pryce
  • Isabelle Weiss

There are no affiliations available

Personalised recommendations