N-METHYL-D-ASPARTIC ACID RECEPTOR ANTAGONIST-INDUCED FREQUENCY OSCILLATIONS IN MICE RECREATE PATTERN OF ELECTROPHYSIOLOGICAL DEFICITS IN SCHIZOPHRENIA
N-METHYL-D-ASPARTIC ACID RECEPTOR ANTAGONIST-INDUCED FREQUENCY OSCILLATIONS IN MICE RECREATE PATTERN OF ELECTROPHYSIOLOGICAL DEFICITS IN SCHIZOPHRENIA
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DOI：
10.1016/j.neuroscience.2008.10.031
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发表时间：
2009-01-23
期刊：
影响因子：
3.3
通讯作者：
Siegel, S. J.
中科院分区：
文献类型：
--
作者：
Ehrlichman, R. S.;Gandal, M. J.;Siegel, S. J.
简介：对听觉刺激的电生理反应为阐明精神疾病的机制和评估治疗提供了有用的手段。精神分裂症患者在配对点击任务期间的门控缺陷以及异常刺激后缺乏失配负性已经得到了很好的表征。最近，对基础频率振荡、诱导频率振荡和诱发频率振荡的分析作为患者和动物模型认知处理的附加测量方法获得了支持。本研究的目的是在 N-甲基-D-天冬氨酸受体 (NMDAR) 功能减退和多巴胺能亢进的背景下检查小鼠在 θ (4-7.5 Hz) 和 γ (31-61 Hz) 频段的频率振荡，这两者都被认为是精神分裂症的药理学模型。 实验程序：脑电图 (EEG) 五个治疗组中的小鼠在听觉任务期间记录的声音，这些治疗组由氟哌啶醇、利培酮、安非他明、氯胺酮或氯胺酮加氟哌啶醇组成。计算两个频率的基础功率、诱导功率和诱发功率。结果：氯胺酮增加了伽马波段的基础功率，降低了θ波段的诱发功率。常规抗精神病药治疗不能阻止基础伽马值的增加。没有其他治疗组能够在小鼠中完全重现这种模式。结论：氯胺酮引起的脑电图功率谱变化与精神分裂症患者报告的 theta 和 gamma 频率范围异常一致。我们的研究结果支持这样的假设：NMDAR 功能减退导致精神分裂症的缺陷，而多巴胺能通路本身可能无法解释这些变化。 (c) 2009 年国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
Introduction: Electrophysiological responses to auditory stimuli have provided a useful means of elucidating mechanisms and evaluating treatments in psychiatric disorders. Deficits in gating during paired-click tasks and lack of mismatch negativity following deviant stimuli have been well characterized in patients with schizophrenia. Recently, analyses of basal, induced, and evoked frequency oscillations have gained support as additional measures of cognitive processing in patients and animal models. The purpose of this study is to examine frequency oscillations in mice across the theta (4-7.5 Hz) and gamma (31-61 Hz) bands in the context of N-methyl-D-aspartic acid receptor (NMDAR) hypofunction and dopaminergic hyperactivity, both of which are thought to serve as pharmacological models of schizophrenia.Experimental procedures: Electroencephalograms (EEG) were recorded from mice in five treatment groups that consisted of haloperidol, risperidone, amphetamine, ketamine, or ketamine plus haloperidol during an auditory task. Basal, induced and evoked powers in both frequencies were calculated.Results: Ketamine increased basal power in the gamma band and decreased the evoked power in the theta band. The increase in basal gamma was not blocked by treatment with a conventional antipsychotic. No other treatment group was able to fully reproduce this pattern in the mice.Conclusions: Ketamine-induced alterations in EEG power spectra are consistent with abnormalities in the theta and gamma frequency ranges reported in patients with schizophrenia. Our findings support the hypothesis that NMDAR hypofunction contributes to the deficits in schizophrenia and that the dopaminergic pathways alone may not account for these changes. (c) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.