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Mutant Mouse Models in Evaluating Novel Approaches to Antipsychotic Treatment

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Novel Antischizophrenia Treatments

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 213))

Abstract

In this review we consider the application of mutant mouse phenotypes to the study of psychotic illness in general and schizophrenia in particular, as they relate to behavioral, psychopharmacological, and cellular phenotypes of putative import for antipsychotic drug development. Mutant models appear to be heuristic at two main levels; firstly, by indicating the functional roles of neuronal components thought to be of relevance to the putative pathobiology of psychotic illness, they help resolve overt behavioral and underlying cellular processes regulated by those neuronal components; secondly, by indicating the functional roles of genes associated with risk for psychotic illness, they help resolve overt behavioral and underlying cellular processes regulated by those risk genes. We focus initially on models of dopaminergic and glutamatergic dysfunction. Then, we consider advances in the genetics of schizophrenia and mutant models relating to replicable risk genes. Lastly, we extend this discussion by exemplifying two new variant approaches in mutant mice that may serve as prototypes for advancing antipsychotic drug development. There is continuing need not only to address numerous technical challenges but also to develop more “real-world” paradigms that reflect the milieu of gene × environment and gene × gene interactions that characterize psychotic illness and its response to antipsychotic drugs.

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Acknowledgments

The authors’ studies are supported by a Science Foundation Ireland Principal Investigator grant (07/IN.1/B960) and a Postdoctoral Fellowship from the Health Research Board of Ireland (PD/2007/20).

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Authors and Affiliations

  1. Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin 2, Ireland

    Colm M. P. O’Tuathaigh, Lieve Desbonnet & John L. Waddington

  2. School of Medicine, University College Cork, Cork, Ireland

    Colm M. P. O’Tuathaigh

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  1. Colm M. P. O’Tuathaigh
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  2. Lieve Desbonnet
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  3. John L. Waddington
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Correspondence to Colm M. P. O’Tuathaigh .

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Editors and Affiliations

  1. Dept. Psychiatry, University of California San Diego, Gilman Drive 9500, La Jolla, 92093-0804, California, USA

    Mark A. Geyer

  2. Institut für Pharmakologie, Universität, Neuroscience Research, Abbott GmbH & Co. KG, Knollstraße, Ludwigshafen, 67061, Germany

    Gerhard Gross

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O’Tuathaigh, C.M.P., Desbonnet, L., Waddington, J.L. (2012). Mutant Mouse Models in Evaluating Novel Approaches to Antipsychotic Treatment. In: Geyer, M., Gross, G. (eds) Novel Antischizophrenia Treatments. Handbook of Experimental Pharmacology, vol 213. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-25758-2_5

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