Motor-evoked potentials after focal electrical stimulation predict drug-induced convulsion potentials in rats
Motor-evoked potentials after focal electrical stimulation predict drug-induced convulsion potentials in rats
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DOI：
10.1080/15376516.2022.2101038
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发表时间：
2022-08-19
影响因子：
3.2
通讯作者：
Fujiki，Minoru
中科院分区：
文献类型：
--
作者：
Kuga，Kazuhiro;Ozaki，Harushige;Fujiki，Minoru
药物引起的惊厥——通常是由GABA受体的抑制和谷氨酸受体的刺激引起的——在动物身上很难预测。在这项研究中，我们尝试在局灶电刺激或使用功能观察电池（FOB）后使用运动诱发电位（MEPs）检测惊厥前电位。戊四唑、肉桂酸和匹罗卡平作为惊厥诱导药物，巴氯芬作为阴性对照。首先，将每种化合物给予雄性大鼠，并进行FOB测试。所有药物均引起行为改变，但没有发现共性。单次电刺激训练记录给药后麻醉60分钟（间隔5分钟）的mep。观察到每种惊厥诱导药物的mep呈剂量依赖性增加。此外，在给药后10分钟，以1 ~ 15 ms的刺激间隔（ISI）对大脑运动皮层进行配对电刺激（条件和测试）。所有惊厥诱导药物均抑制短间期皮质内抑制（ISI: 3 ms），这可能与GABA有关。与谷氨酸相关的皮质内促进作用（ISI: 11 ms）未被任何药物增强，而被匹罗卡品抑制。任何药物的短间隔皮质内抑制或皮质内促进均未发现剂量相关性。巴氯芬给药后mep未见变化。这些结果表明，使用MEP来评估抽搐电位及其相关机制是可能的，而不依赖于行为改变。使用该模型早期识别抽搐电位将导致更有效的药物开发。
Drug-induced convulsions—often caused by the inhibition of GABA receptors and stimulation of glutamate receptors—are difficult to predict in animals. In this study, we attempted to detect the proconvulsant potential using motor-evoked potentials (MEPs) after focal electrical stimulation or upon using a functional observational battery (FOB). Pentylenetetrazole, kainic acid, and pilocarpine were used as convulsion-inducing drugs, and baclofen was used as a negative control. First, each compound was administered to male rats, and the FOB tests were performed. All drugs induced behavioral changes, but no commonality was found. Single electrical stimulation train MEPs were recorded under anesthesia for 60 min (at 5 min intervals) after administration of each drug. A dose-dependent increase in MEPs was observed for each convulsion-inducing drug. Moreover, paired electrical stimulation (conditioned and test) of the cerebral motor cortex was conducted with a 1–15 ms interstimulus interval (ISI), 10 min after administration of the drug. All convulsion-inducing drugs inhibited the short-interval intracortical inhibition (ISI: 3 ms), which may be associated with GABA. Intracortical facilitation (ISI: 11 ms), related to glutamate, was not enhanced by any drug but was inhibited by pilocarpine. Dose correlation was not found in short-interval intracortical inhibition or intracortical facilitation in any drugs. No changes in MEPs were observed after baclofen administration. These results suggest that it is possible to evaluate the convulsion potential and associated mechanisms using MEP, independent of the behavioral changes. The early identification of convulsion potential using this model will lead to more efficient drug development.