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

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54 Citations (Scopus)

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 lpa 1 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 in vitro 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 lpa 1 (-/-) mice. Fast cyclic voltammetry measurements in the dorsal raphe nucleus demonstrated significant decreases in electrically evoked 5-HT efflux in lpa 1 (-/-) mice. In summary, these data demonstrate that the lpa 1 mutation produces a number of changes in neurotransmitters that have been associated with a schizophrenic-like pathology.

Original languageEnglish
Pages (from-to)371-377
Number of pages7
JournalNeurochemical Research
Volume30
Issue number3
DOIs
Publication statusPublished - 1 Mar 2005

Keywords

  • 5-HT
  • GABA
  • Glutamate
  • Release
  • Voltammetry

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