Please use this identifier to cite or link to this item:
|Title:||Sensitivity to MK-801 in phospholipase C-Β1 knockout mice reveals a specific NMDA receptor deficit|
|Authors:||Gray, L. |
|Citation:||Gray, L., McOmish, C.E., Scarr, E., Dean, B., Hannan, A.J. (2009-08). Sensitivity to MK-801 in phospholipase C-Β1 knockout mice reveals a specific NMDA receptor deficit. International Journal of Neuropsychopharmacology 12 (7) : 917-928. ScholarBank@NUS Repository. https://doi.org/10.1017/S1461145709009961|
|Abstract:||Phospholipase C-1 (PLC-1) is a critical component of multiple signalling pathways downstream of neurotransmitter receptors. Mice lacking this enzyme display a striking behavioural phenotype with relevance to human psychiatric disease. Glutamatergic dysfunction is strongly associated with several abnormal behavioural states and may underlie part of the phenotype of the phospholipase C-1 knockout (KO) mouse. A heightened response to glutamatergic psychotomimetic drugs is a critical psychosis-related endophenotype, and in this study it was employed as a correlate of glutamatergic dysfunction. Control (n=8) and PLC-1 KO mice (n=6) were treated with MK-801, a NMDA receptor (NMDAR) antagonist, following either standard housing or environmental enrichment, and the motor function and locomotor activity thus evoked was assessed. In addition, MK-801 binding to the NMDAR was evaluated through radioligand autoradiography in post-mortem tissue (on a drug-naive cohort). We have demonstrated a significantly increased sensitivity to the effects of the NMDA antagonist MK-801 in the PLC-1 KO mouse. In addition, we found that this mouse line displays reduced hippocampal NMDAR expression, as measured by radioligand binding. We previously documented a reversal of specific phenotypes in this mouse line following housing in an enriched environment. Enrichment did not alter this heightened MK-801 response, nor NMDAR expression, indicating that this therapeutic intervention works on specific pathways only. These findings demonstrate the critical role of the glutamatergic system in the phenotype of the PLC-1 KO mouse and highlight the role of these interconnected signalling pathways in schizophrenia-like behavioural disruption. These results also shed further light on the capacity of environmental factors to modulate subsets of these phenotypes. Copyright © 2009 CINP.|
|Source Title:||International Journal of Neuropsychopharmacology|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Jan 23, 2019
WEB OF SCIENCETM
checked on Jan 7, 2019
checked on Dec 21, 2018
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.