Neurochemical changes in LPA1 receptor deficient mice -: A putative model of schizophrenia

LPA(1) is a G(i)-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.