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

doi:10.1007/s11064-005-2611-6

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

Drug Discovery Biology

Research output: Contribution to journal › Article › Research › peer-review

55 Citations (Scopus)

Abstract

LPA₁ 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.

Original language	English
Pages (from-to)	371-377
Number of pages	7
Journal	Neurochemical Research
Volume	30
Issue number	3
DOIs	https://doi.org/10.1007/s11064-005-2611-6
Publication status	Published - 1 Mar 2005

Keywords

5-HT
GABA
Glutamate
Release
Voltammetry

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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.",

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author = "Claire Roberts and Panida Winter and Shilliam, {Claire S.} and Hughes, {Zoe A.} and Christopher Langmead and Maycox, {Peter R.} and Dawson, {Lee A.}",

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AU - Winter, Panida

AU - Shilliam, Claire S.

AU - Hughes, Zoe A.

AU - Langmead, Christopher

AU - Maycox, Peter R.

AU - Dawson, Lee A.

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AB - 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.

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

Abstract

Keywords

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