Mice with reduced NMDA receptor expression display behaviors related to schizophrenia

被引:835
作者
Mohn, AR
Gainetdinov, RR
Caron, MG
Koller, BH [1 ]
机构
[1] Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA
[3] Duke Univ, Med Ctr, Howard Hughes Med Inst Labs, Dept Cell Biol & Med, Durham, NC 27710 USA
关键词
D O I
10.1016/S0092-8674(00)81972-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
N-methyl-D-aspartate receptors (NMDARs) represent a subclass of glutamate receptors that play a critical role in neuronal development and physiology. We report here the generation of mice expressing only 5% of normal levels of the essential NMDAR1 (NR1) subunit. Unlike NR1 null mice, these mice survive to adulthood and display behavioral abnormalities, including increased motor activity and stereotypy and deficits in social and sexual interactions. These behavioral alterations are similar to those observed in pharmacologically induced animal models of schizophrenia and can be ameliorated by treatment with haloperidol or clozapine, antipsychotic drugs that antagonize dopaminergic and serotonergic receptors. These findings support a model in which reduced NMDA receptor activity results in schizophrenic-like behavior and reveals how pharmacological manipulation of monoaminergic pathways can affect this phenotype.
引用
收藏
页码:427 / 436
页数:10
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