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用于评估假定认知增强剂对小鼠影响的T型迷宫连续交替任务。

The T-maze continuous alternation task for assessing the effects of putative cognition enhancers in the mouse.

作者信息

Spowart-Manning L, van der Staay F J

机构信息

Department of Anatomy, School of Medical Sciences, University of Bristol, Bristol, UK.

出版信息

Behav Brain Res. 2004 May 5;151(1-2):37-46. doi: 10.1016/j.bbr.2003.08.004.

DOI:10.1016/j.bbr.2003.08.004
PMID:15084419
Abstract

The T-maze continuous alternation task (T-CAT) assesses the spatial exploratory performance in mice. We performed a series of four experiments in order to establish the T-CAT in mice in our laboratory, to replicate published findings, and to investigate the effects of scopolamine and donepezil. In the first experiment, the task was found to be sensitive to differences between mouse strains, corroborating findings reported by Gerlai. HsdWin:CFW1 mice alternated below chance level, C57BL/6JIco and B6D2F1/JIco mice performed above chance level, and C57BL/6NTac and 129S6/SvEvTac mice performed at chance level. In the second experiment, donepezil (Aricept, E2020) at the dose of 3 mg/kg p.o. increased the rate of alternations above the level of the vehicle-treated control group in C57BL/6JIco mice, suggesting that this drug can act as cognition enhancer in normal animals. 1mg/kg scopolamine, administered intraperiteoneally (i.p.), impaired the spontaneous alternation behaviour of the mice. The slightly lower dose of 0.75 mg/kg did not affect alternation performance. The high dose of donepezil (3 mg/kg) was able to antagonise the scopolamine-induced performance deficit. With respect to time to complete a session, the results were inconclusive. In the third experiment, we found that scopolamine, administered i.p. at the dose of 1 mg/kg, or subcutaneously (s.c.) at the dose of 0.1 mg/kg, decreased the rate of spontaneous alternations in C57BL mice in the T-CAT and increased the time to complete a session. Most likely due to adverse side effects induced by the dose of 1mg/kg scopolamine, 4 out of 10 animals did not complete at least eight free-choice trials during the maximum session duration of 30min. No such adverse effects were seen after 0.1 mg/kg scopolamine, administered s.c. Finally, we evaluated whether the T-CAT yields replicable results. We conclude that the T-CAT provides a reliable tool for assessing the effects of cognition-modulating treatments in mice.

摘要

T 型迷宫连续交替任务(T-CAT)用于评估小鼠的空间探索能力。我们进行了一系列四个实验,目的是在我们实验室中建立小鼠的 T-CAT,重复已发表的研究结果,并研究东莨菪碱和多奈哌齐的作用。在第一个实验中,发现该任务对小鼠品系之间的差异敏感,这与 Gerlai 报道的结果一致。HsdWin:CFW1 小鼠的交替次数低于随机水平,C57BL/6JIco 和 B6D2F1/JIco 小鼠的表现高于随机水平,而 C57BL/6NTac 和 129S6/SvEvTac 小鼠的表现处于随机水平。在第二个实验中,口服剂量为 3 mg/kg 的多奈哌齐(安理申,E2020)使 C57BL/6JIco 小鼠的交替率高于溶剂处理对照组的水平,表明该药物可作为正常动物的认知增强剂。腹腔注射(i.p.)1mg/kg 的东莨菪碱会损害小鼠的自发交替行为。剂量稍低的 0.75 mg/kg 不影响交替表现。高剂量的多奈哌齐(3 mg/kg)能够拮抗东莨菪碱诱导的行为缺陷。关于完成一个实验环节的时间,结果尚无定论。在第三个实验中,我们发现腹腔注射 1 mg/kg 或皮下注射(s.c.)0.1 mg/kg 的东莨菪碱会降低 C57BL 小鼠在 T-CAT 中的自发交替率,并增加完成一个实验环节的时间。很可能是由于 1mg/kg 东莨菪碱剂量引起的不良副作用,在 30 分钟的最长实验环节持续时间内,10 只动物中有 4 只没有完成至少八次自由选择试验。皮下注射 0.1 mg/kg 东莨菪碱后未观察到此类不良影响。最后,我们评估了 T-CAT 是否能产生可重复的结果。我们得出结论,T-CAT 为评估认知调节治疗对小鼠的影响提供了一个可靠的工具。

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