Please use this identifier to cite or link to this item: https://doi.org/10.1017/S1461145708009085
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dc.titleClozapine reverses schizophrenia-related behaviours in the metabotropic glutamate receptor 5 knockout mouse: Association with N-methyl-d-aspartic acid receptor up-regulation
dc.contributor.authorGray, L.
dc.contributor.authorVan Den Buuse, M.
dc.contributor.authorScarr, E.
dc.contributor.authorDean, B.
dc.contributor.authorHannan, A.J.
dc.date.accessioned2016-11-08T08:22:54Z
dc.date.available2016-11-08T08:22:54Z
dc.date.issued2009-02
dc.identifier.citationGray, L., Van Den Buuse, M., Scarr, E., Dean, B., Hannan, A.J. (2009-02). Clozapine reverses schizophrenia-related behaviours in the metabotropic glutamate receptor 5 knockout mouse: Association with N-methyl-d-aspartic acid receptor up-regulation. International Journal of Neuropsychopharmacology 12 (1) : 45-60. ScholarBank@NUS Repository. https://doi.org/10.1017/S1461145708009085
dc.identifier.issn14611457
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/129465
dc.description.abstractAbstract Abnormalities in glutamatergic signalling are proposed in schizophrenia in light of the schizophreniform psychosis elicited by NMDA antagonists. The metabotropic glutamate receptor 5 (mGluR5) interacts closely with the NMDA receptor and is implicated in several behavioural endophenotypes of schizophrenia. We have demonstrated that mice lacking mGluR5 have increased sensitivity to the hyperlocomotive effects of the NMDA antagonist MK-801. Mice lacking mGluR5 also show abnormal locomotor patterns, reduced prepulse inhibition (PPI), and deficits on performance of a short-term spatial memory task on the Y-maze. Chronic administration of the antipsychotic drug clozapine ameliorated the locomotor disruption and reversed the PPI deficit, but did not improve Y-maze performance. Chronic clozapine increased NMDA receptor binding ([3H]MK-801) but did not alter dopamine D2 ([3H]YM-09151), 5-HT2A ([3H]ketanserin), or muscarinic M1/M4 receptor ([ 3H]pirenzepine), binding in these mice. These results demonstrate behavioural abnormalities that are relevant to schizophrenia in the mGluR5 knockout mouse and a reversal of behaviours with clozapine treatment. These results highlight both the interactions between mGluR5 and NMDA receptors in the determination of schizophreniform behaviours and the potential for the effects of clozapine to be mediated by NMDA receptor regulation. © 2008 CINP.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1017/S1461145708009085
dc.sourceScopus
dc.subjectAntipsychotic
dc.subjectBehaviour
dc.subjectMGluR5
dc.subjectNMDA
dc.typeArticle
dc.contributor.departmentDUKE-NUS GRADUATE MEDICAL SCHOOL S'PORE
dc.description.doi10.1017/S1461145708009085
dc.description.sourcetitleInternational Journal of Neuropsychopharmacology
dc.description.volume12
dc.description.issue1
dc.description.page45-60
dc.description.codenIJNUF
dc.identifier.isiut000262552700005
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