Please use this identifier to cite or link to this item: https://doi.org/10.1017/S1461145708009085
Title: Clozapine reverses schizophrenia-related behaviours in the metabotropic glutamate receptor 5 knockout mouse: Association with N-methyl-d-aspartic acid receptor up-regulation
Authors: Gray, L. 
Van Den Buuse, M.
Scarr, E.
Dean, B.
Hannan, A.J.
Keywords: Antipsychotic
Behaviour
MGluR5
NMDA
Issue Date: Feb-2009
Citation: Gray, 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
Abstract: Abstract 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.
Source Title: International Journal of Neuropsychopharmacology
URI: http://scholarbank.nus.edu.sg/handle/10635/129465
ISSN: 14611457
DOI: 10.1017/S1461145708009085
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

74
checked on Sep 13, 2018

WEB OF SCIENCETM
Citations

68
checked on Sep 5, 2018

Page view(s)

10
checked on Jul 19, 2018

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.