Neurochemical Research

, Volume 30, Issue 3, pp 371–377

Neurochemical Changes in LPA1 Receptor Deficient Mice – A Putative Model of Schizophrenia

  • Claire Roberts
  • Panida Winter
  • Claire S. Shilliam
  • Zoe A. Hughes
  • Christopher Langmead
  • Peter R. Maycox
  • Lee A. Dawson
Article

Abstract

LPA1 is a Gi-coupled seven transmembrane receptor with high affinity for the ligand lysophosphatidic acid. We have investigated the effect of targeted deletion at the lpa1 locus on evoked release of amino acids from hippocampal slices, using in vitro superfusion techniques, and evoked 5-HT efflux from the dorsal raphe nucleus, using invitro fast cyclic voltammetry. Superfusion of hippocampal slices revealed that basal levels of tyrosine, aspartate and glutamate release were significantly increased while K+-evoked release of glutamate and GABA were significantly decreased in lpa1(−/−) mice. Fast cyclic voltammetry measurements in the dorsal raphe nucleus demonstrated significant decreases in electrically evoked 5-HT efflux in lpa1(−/−) mice. In summary, these data demonstrate that the lpa1 mutation produces a number of changes in neurotransmitters that have been associated with a schizophrenic-like pathology.

Keywords

5-HT GABA glutamate release voltammetry 

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Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • Claire Roberts
    • 1
  • Panida Winter
    • 1
  • Claire S. Shilliam
    • 1
  • Zoe A. Hughes
    • 1
  • Christopher Langmead
    • 1
  • Peter R. Maycox
    • 1
  • Lee A. Dawson
    • 1
  1. 1.Psychiatry Centre of Excellence for Drug DiscoveryGlaxoSmithKlineEssexUK

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