Mohn A R, Gainetdinov R R, Caron M G, Koller B H
Department of Medicine, University of North Carolina at Chapel Hill 27599. USA.
Cell. 1999 Aug 20;98(4):427-36. doi: 10.1016/s0092-8674(00)81972-8.
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.
N-甲基-D-天冬氨酸受体（NMDARs）是谷氨酸受体的一个亚类，在神经元发育和生理学中起关键作用。我们在此报告了仅表达正常水平5%必需NMDAR1（NR1）亚基的小鼠的产生。与NR1基因敲除小鼠不同，这些小鼠能存活至成年，并表现出行为异常，包括运动活动增加、刻板行为以及社交和性互动缺陷。这些行为改变类似于在药理学诱导的精神分裂症动物模型中观察到的改变，并且可用氟哌啶醇或氯氮平（拮抗多巴胺能和5-羟色胺能受体的抗精神病药物）治疗来改善。这些发现支持了一种模型，即NMDA受体活性降低导致精神分裂症样行为，并揭示单胺能途径的药理学操纵如何影响这种表型。
