Intrastrain differences in seizure susceptibility, pharmacological response and basal neurochemistry of Wistar rats

Intrastrain differences in seizure susceptibility, pharmacological response and basal neurochemistry of Wistar rats
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DOI:
10.1016/j.eplepsyres.2009.09.009
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发表时间:
2009-12-01
期刊:
影响因子:
2.2
通讯作者:
Clinckers, Ralph
Clinckers, Ralph
中科院分区:
医学4区
文献类型:
--
作者:
Portelli, Jeanelle;Aourz, Najat;Clinckers, Ralph

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为了更好地了解潜在的病理生理机制以及筛选潜在的抗惊厥药物,需要可靠的良好表征的癫痫发作动物模型。我们目前使用局灶性毛果芸香碱模型作为急性边缘系统癫痫发作模型。由于供应商的繁殖问题,以及毛果芸香碱诱导的癫痫易感性的明显变化,我们被迫在2年内改变繁殖地点和供应商。雄性Wistar大鼠购自Charles River Laboratories(法国和德国)的两个饲养地点,或购自哈兰实验室(荷兰)。在本回顾性研究中,我们评价了这些供应商变更对氯胺酮给药(以建立麻醉)、对匹鲁卡品诱导的癫痫发作易感性以及对我们研究中所有匹鲁卡品给药大鼠的基础细胞外海马去甲肾上腺素、多巴胺、5-羟色胺、γ-氨基丁酸和谷氨酸水平的影响。所有分析参数均存在显著差异。本研究清楚地表明,不同供应商/饲养地点之间,甚至同一饲养地点的大鼠之间,确实存在品系内差异。(C)2009 Elsevier B. V.保留所有权利。
Reliable well-characterised animal models of seizures are necessary in order to better understand the underlying pathophysiological mechanisms as well as to screen potential anticonvulsant drugs. We currently use the focal pilocarpine model as an acute limbic seizure model. Due to breeding problems at the vendor, and apparent changes in pilocarpine-induced seizure susceptibility, we were forced to change breeding locations and vendors over a period of 2 years. Mate Wistar rats were either purchased from two breeding locations of Charles River Laboratories (France and Germany), or obtained from Harlan Laboratories (The Netherlands). In the present retrospective study we evaluated the impact of these vendor changes on ketamine dosing to establish anaesthesia, on pilocarpine-induced seizure susceptibility, and on basal extracellular hippocampal noradrenaline, dopamine, serotonin, gamma-amino butyric acid, and glutamate levels of all pilocarpine-treated rats included in our studies. Significant differences were present in all of the parameters analyzed. This study clearly illustrates that intrastrain differences do exist from one vendor/breeding location to another, or even between rats from the same breeding location. (C) 2009 Elsevier B.V. All rights reserved.