, Volume 30, Issue 3, pp 371-377

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

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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.