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Modeling Schizophrenia: Focus on Developmental Models

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In Vivo Neuropharmacology and Neurophysiology

Part of the book series: Neuromethods ((NM,volume 121))

Abstract

Schizophrenia is a chronic, severe and disabling brain disorder that affects more than 21 million people around the world. Despite a tremendous amount of research effort, the etiopathology of schizophrenia is little understood. Reliable and predictive animal models are essential to increase our understanding of the neurobiological basis of the disorder and for the development of novel antipsychotics with improved therapeutic efficacy and tolerable side effects. A favorite working hypothesis is the so-called two-hit theory. Developmental animal models of schizophrenia are a valuable heuristic tool which focuses on this aspect. Manipulations of the environment, drug administration, or discrete surgical intervention during the sensitive prenatal or postnatal period induce a reorganization of neuronal circuits resulting in irreversible changes in central nervous system (CNS) function, which typically appear after puberty. These models are considered superior, since they can include different schizophrenia-relevant brain and behavioral pathologies and incorporate the developmental component of the disorder.

This review aims to summarize methodological and predictive aspects of three developmental animal models for research on schizophrenia.

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Authors and Affiliations

  1. Faculty of Medicine, Institute of Pharmacology and Toxicology, O.-v.-Guericke University, Leipziger Str. 44, 39120, Magdeburg, Germany

    Axel Becker

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  1. Axel Becker
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Correspondence to Axel Becker .

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Editors and Affiliations

  1. Department of Pharmacology and Toxicology, University of Innsbruck, Innsbruck, Austria

    Athineos Philippu

Appendices

Appendix 1

A comprehensive and highly detailed description of the essential materials and methods for producing the lesion, lesion verification, and a discussion of trouble areas and pitfalls has been given by Chambers and Lipska [151]. This chapter also includes some instructive illustrations. A study of this will enable the reader to perform perfect lesioning and, moreover, to adapt the method for the purpose of conducting further investigations in the field of schizophrenia research.

Appendix 2

Neonatal brain lesions have not been implicated in causing schizophrenia, and therefore this model lacks construct validity . In other experiments, the effects of transient inactivation of the ventral hippocampus during a critical period of development using either tetrodotoxin [117] or lidocaine [128, 152] were studied. After puberty, the rats with neonatal ventral transient inactivation exhibited alterations in behavior which were not evident in rats with adult ventral hippocampus inactivation. Among these, behavioral pattern hyperlocomotion, increased activity in response to amphetamine , and disrupted latent inhibition were reported. Interestingly, social behavior was not altered in rats with neonatal tetrodotoxin inactivation [117] but certainly was altered in rats whose ventral hippocampus was transiently inactivated with lidocaine [152]. It is not understood how such a transient and restricted blockade of ventral hippocampal activity in neonatal life can permanently alter brain function. It was concluded that transient ventral hippocampus inactivation might represent a potential new model of aspects of schizophrenia without a gross anatomical lesion [117].

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Becker, A. (2017). Modeling Schizophrenia: Focus on Developmental Models. In: Philippu, A. (eds) In Vivo Neuropharmacology and Neurophysiology. Neuromethods, vol 121. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6490-1_16

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  • DOI: https://doi.org/10.1007/978-1-4939-6490-1_16

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