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使用计算机化定量脑电图筛选实验大鼠药物和化学物质效应的方法

Method for screening drug and chemical effects in laboratory rats using computerized quantitative electroencephalography.

作者信息

Jones R D, Sheets L P, Mueller R E

机构信息

Toxicology Department, Bayer Corporation, Stilwell, KS 66085-9104, USA.

出版信息

Vet Hum Toxicol. 1995 Dec;37(6):521-7.

PMID:8588286
Abstract

A minimally-invasive method of quantitative electroencephalography (qEEG) that requires no anesthetics and parallels techniques of naturalistic stimulation was developed and validated for regulatory testing of drugs and chemicals in rats. Male and female Fischer 344 rats were utilized in a randomized-block design to measure qEEG target parameters associated with a range of cholinesterase inhibition. For this study, physostigmine was administered ip at doses of 0.05, 0.2 or 1.0 mg/kg, resulting in average cholinesterase inhibition in plasma (28, 38 and 70%), erythrocytes (19, 24 and 36%), and brain (2, 10 and 31%) which correlated well with increased total power and amplitude changes. Additional treatment-related effects consisted of decreased relative alpha and beta, increased relative delta, and a left-shift in the spectral-edge frequency. In a second study, male and female Sprague-Dawley rats were utilized in a treatment-by-subjects design to determine qEEG target parameter changes due to the M2 autoreceptor agonist oxotremorine. Repeated incremental doses (0.05, 0.1, 0.2 mg/kg; ip) of oxotremorine resulted in increased beta contribution, a right-shift in the spectral-edge frequency and decreased alpha contribution. These qEEG results with physostigmine and oxotremorine correlate well with receptor-specific and general muscarinic effects, making it a reliable contribution to analysis of agonist and antagonist effects of cholinergic compounds.

摘要

一种无需麻醉且与自然刺激技术相似的定量脑电图(qEEG)微创方法被开发出来,并在大鼠药物和化学品监管测试中得到验证。采用随机区组设计,利用雄性和雌性Fischer 344大鼠来测量与一系列胆碱酯酶抑制相关的qEEG目标参数。在本研究中,毒扁豆碱以0.05、0.2或1.0 mg/kg的剂量腹腔注射,导致血浆(28%、38%和70%)、红细胞(19%、24%和36%)和大脑(2%、10%和31%)中的胆碱酯酶平均抑制,这与总功率增加和振幅变化密切相关。其他与治疗相关的效应包括相对α和β波减少、相对δ波增加以及频谱边缘频率左移。在第二项研究中,采用受试者治疗设计,利用雄性和雌性Sprague-Dawley大鼠来确定M2自受体激动剂氧化震颤素引起的qEEG目标参数变化。氧化震颤素重复递增剂量(0.05、0.1、0.2 mg/kg;腹腔注射)导致β波贡献增加、频谱边缘频率右移以及α波贡献减少。毒扁豆碱和氧化震颤素的这些qEEG结果与受体特异性和一般毒蕈碱效应密切相关,使其成为胆碱能化合物激动剂和拮抗剂效应分析的可靠贡献。

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