多巴胺激动剂阿朴吗啡对东莨菪碱诱导小鼠学习记忆障碍的影响  

Effect of dopamine receptor agonist apomorphine on scopolamine induced memory deficits in mice

作　　者：杨慧娣[1] 杨铮[1] 刘陶迪[1] 

机构地区：[1]内蒙古医科大学基础医学院,呼和浩特010110

出　　处：《中国应用生理学杂志》2014年第3期259-263,共5页Chinese Journal of Applied Physiology

基　　金：内蒙古医科大学博士启动基金(bsjj201306)

摘　　要：目的:研究多巴胺(DA)对小鼠学习记忆障碍的影响及其机制。方法:实验1采用腹腔注射东莨菪碱0.3 mg/kg(SCOP 0.3,n=10)和3.0 mg/kg(SCOP 3.0),连续注射60 d,在第53天和60天用避暗法测定记忆行为,第60天处死动物后取脑用免疫组化的方法测定TH-ir和Fos-ir的表达。实验2根据实验1结果造小鼠记忆障碍的模型后将小鼠分成4组,1组腹腔注射生理盐水(NS),其他3组腹腔注射阿朴吗啡0.1 mg/kg(APO 0.1)、0.5 mg/kg(APO 0.5)和2.0 mg/kg(APO 2.0),每组10只动物,连续30 d。在注射阿朴吗啡第23天和30天测定避暗行为。第30天处死动物后取脑用免疫组化的方法测定Fos-ir和TH-ir的表达。结果:避暗法测定记忆发现东莨菪碱抑制小鼠的记忆。第60天,东莨菪碱3.0 mg/kg组(SCOP 3.0)的潜伏期比NS组显著缩短,仅是NS组的1/4(P>0.05),错误次数比NS组增加了大约4倍(P>0.05),SCOP 0.3组的潜伏期和错误次数与NS组没有明显差异。免疫组化结果表明在伏隔核和海马区的CA1和CA3的Fos-ir细胞数明显降低(P<0.01),且被盖腹侧区的酪氨酸羟化酶(TH-ir)和共表达TH/Fos-ir细胞显著减少(P<0.01)。注射阿朴吗啡后明显缓解了小鼠的记忆障碍,且腹侧被盖区TH-ir细胞增加(P<0.05)。结论:阿朴吗啡明显减轻东莨菪碱诱导的小鼠记忆障碍,是通过增强腹侧被盖区多巴胺神经元的活性来实现的。Objective： To research the mechanism of dopamine （DA） controlled memory in mice. Methods： Mice received i.p. injection of scopolamine （0.3 mg/kg, SCOP 0.3, and 3.0mg/kg, SCOP 3.0, respectively, n = 10） and saline （NS, n = 10） for 60 days in experiment 1. Memory of mice was detected by dark avoidance behavior in the 53^rd d and the 60^th d. Animals were sacrificed after the memory test; brain tissues were processed for Fos-ir and TH-ir by immunohistochemistry. Mice were divided into four groups according results of expriment 1, they received i.p. injection of apomorphine （0.1mg/kg, APO 0.1, 0.5 mg/kg, APO 0.5, and 2.0 mg/kg, APO 2.0 respectively, n = 10）. Results： Memory was inhibited in mice injected scopolamine 3.0 mg/kg. Latency was signitlcanfly less than in NS group, only 1/ 4 that of NS group （ P 〉 0.05）. The number of mistake of SCOP 3.0 group increased about four times than that of NS group （P 〉 0.05）. But there was no difference of latency and number of mistake between SCOP 0.3 and NS group in expriment 1. Scopolamine-induced memory deficit was associated with decreased cellular activation, indicated by Fos immtmoreactive （ir） staining, in NAcc CA1 and CA3 （ P〈 0.05）, and also associated with decreases in the number of cells labeled for tyrosine hydroxylase （TH-ir）, the rate limiting enzyme for dopamine conversion（ P 〈 0.01 ） and the number of cells co-labeled for TH-ir/Fos-ir （ P 〈 0.01 ） in the ventral tegmental area（VTA）, apomorphine lessened scopolamine-induced memory deficit in experiment 2. The number of cells co-labeled for TH-ir/Fos-ir （ P 〈 0.05） was increased in VTA after apomorphine treatment. Conclusion： Apomorphine lessened scopolamine-induced memory deficit in mice by increasing DA activities in VTA.

关 键 词：东莨菪碱 记忆障碍 多巴胺 阿朴吗啡 

分 类 号：R73-3[医药卫生—肿瘤]