摘要
巴氯芬(baclofen)是临床上唯一使用的γ-氨基丁酸B型受体(γ-aminobutyric acid type B receptor,GABA_(B) receptor)激动剂,现有报道发现其能够影响小鼠的认知功能,但研究结果却存在差异。此前研究所使用的范式,如水迷宫、八臂迷宫等,均涉及奖惩效应。为了避免奖惩对小鼠行为表现的影响,本研究使用了一种基于啮齿类动物自然探索天性的Y迷宫,以探讨不同剂量的巴氯芬(1.0 mg/kg、2.5 mg/kg、7.5 mg/kg)对小鼠空间认知功能的影响,并使用旷场实验检测该药物不同剂量对小鼠自主活动和焦虑程度的影响。结果表明,中、高剂量的巴氯芬(2.5 mg/kg、7.5 mg/kg)不同程度地损伤了小鼠对Y迷宫新异臂的识别能力,高剂量的巴氯芬(7.5 mg/kg)能够损伤小鼠在旷场中的运动能力和探索能力,但所有剂量都不影响小鼠的焦虑程度。本研究揭示了巴氯芬能够剂量依赖性地损伤小鼠的空间识别记忆能力,表明在临床应用上应注意高剂量药物对认知神经系统的影响,避免对其产生损伤。
Baclofen is the only clinically available γ-aminobutyric acid type B receptor(GABA_(B) receptor)agonist.There are reports that baclofen has different effects on cognition,but the research results are controversial.The paradigms used in these studies include Morris water maze and the radial maze,in which reward and punishment effects are involved.In order to avoid the influence of reward and punishment on the behavior of mice,a two-trial Y-maze,which is based on the innate tendency of rodents to explore novel environments,was used to investigate the effects of baclofen(doses 1.0 mg/kg,2.5 mg/kg and 7.5 mg/kg)on spatial recognition memory.An open field test was used to assess the behavior performance of mice under the influence of these doses of baclofen.The results showed that the higher doses of baclofen(2.5 mg/kg and 7.5 mg/kg)impaired the memory performance of mice in the Y-maze task,and the highest dose(7.5 mg/kg)decreased the locomotion and exploration of mice in the open field test.In addition,all used doses did not obviously affect the degree of anxiety in mice.These data suggested that baclofen may dose-dependently impair spatial memory and its negative effects on cognition should be considered in future clinical trials.
作者
周正
宋美慧
褚光辉
付玉
ZHOU Zheng;SONG Mei-hui;CHU Guang-hui;FU Yu(Medical School,Kunming University of Science&Technology,Kunming 650500,Yunnan,China)
出处
《生命科学研究》
CAS
CSCD
2022年第3期213-218,共6页
Life Science Research
基金
国家自然科学基金资助项目(81760258,81560221)
云南省应用基础研究基金项目(2017FB125)
云南省“万人计划”青年拔尖人才专项资助项目。