Neurochemical changes in LPA1 receptor deficient mice--a putative model of schizophrenia.
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 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 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.
Roberts
Claire
C
Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, CM19 5AW, Harlow, Essex, UK. Claire_2_Roberts@gsk.com
Winter
Panida
P
Shilliam
Claire S
CS
Hughes
Zoe A
ZA
Langmead
Christopher
C
Maycox
Peter R
PR
Dawson
Lee A
LA
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D004558:Electric Stimulation; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D018377:Neurotransmitter Agents / Q000378:metabolism; D011903:Raphe Nuclei / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000172:deficiency* / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D012701:Serotonin / Q000378:metabolism
D000596:Amino Acids; D018377:Neurotransmitter Agents; D049368:Receptors, Lysophosphatidic Acid; D012701:Serotonin