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Assessment of a prepulse inhibition deficit in a mutant mouse lacking mGlu5 receptors

Molecular Psychiatry volume 9, pages 35–41 (2004)Cite this article

Abstract

The glutamate hypothesis of schizophrenia derived from evidence that phencyclidine, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, produces schizophrenia-like symptoms in healthy humans. Sensorimotor gating, measured by prepulse inhibition (PPI), is a fundamental form of information processing that is deficient in schizophrenia patients and rodents treated with NMDA antagonists. Hence, PPI is widely used to study the neurobiology of schizophrenia. As the use of PPI as a model of gating deficits in schizophrenia has become more widespread, it has become increasingly important to assess such deficits accurately. Here we identify a possible role of mGluR5 in PPI by using wild type (WT) and mGluR5 knockout (KO) mice of two different background strains, 129SvPasIco and C57BL/6. In both strains, PPI was disrupted dramatically in the mGluR5 KO mice throughout a range of interstimulus intervals and sensory modalities. The present findings further support the glutamate hypothesis of schizophrenia and identify a functional role for mGluR5 in sensorimotor gating.

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Acknowledgements

SAB was supported by MH12961. SCD was supported by MH12249. This work was supported by DA02925 and MH42228 to MAG. MAG holds an equity interest in San Diego Instruments.

Author information

Author notes

  1. S C Dulawa

    Present address: Center for Neurobiology & Behavior, Columbia University, New York, NY, 10032, USA

  2. F Conquet

    Present address: Addex Pharmaceuticals, 1228 Plan les Ouates, Geneva, Switzerland

Authors and Affiliations

  1. Department of Neuroscience, University of California, San Diego, La Jolla, CA, USA

    S A Brody, S C Dulawa & M A Geyer

  2. GlaxoWellcome Experimental Research, IBCM, University of Lausanne, Lausanne, Switzerland

    F Conquet

  3. Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA

    M A Geyer

Authors
  1. S A Brody
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  2. S C Dulawa
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  3. F Conquet
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  4. M A Geyer
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Corresponding author

Correspondence to M A Geyer.

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Brody, S., Dulawa, S., Conquet, F. et al. Assessment of a prepulse inhibition deficit in a mutant mouse lacking mGlu5 receptors. Mol Psychiatry 9, 35–41 (2004). https://doi.org/10.1038/sj.mp.4001404

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  • DOI: https://doi.org/10.1038/sj.mp.4001404

Keywords

  • PPI
  • metabotropic glutamate
  • mGluR5
  • startle
  • prepulse inhibition
  • knockout mouse

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