摘要
目的建立固定比率为10(FR10)的大鼠可卡因药物辨别模型,进行可卡因辨别效应和剂量关系的测试及半数有效量(ED50)测定。方法采用FR值逐渐递增1和每获得5次奖励FR值自动增加1的两种实验程序对32只SD大鼠进行食物训练,食物训练成功的大鼠给予可卡因10 mg·kg^(-1)或氯化钠注射液进行辨别训练;将辨别训练成功的大鼠依次给予可卡因0、0.1、0.5、1.25、2.5、5、10 mg·kg^(-1)进行替代测试,并计算ED50值。结果有27只大鼠食物训练成功进入到辨别训练阶段。采用FR值1、2、4、6、10渐进递增的程序,用时(27.2±2.9) d共19只大鼠辨别训练成功。用可卡因0、0.1、0.5、1.25、2.5、5、10 mg·kg^(-1)进行14只大鼠的替代测试,可卡因踏板反应百分数分别为(18.7±25.1)%、(2.1±4.0)%、(16.1±37.3)%、(36.4±45.9)%、(57.1±48.8)%、(74.3±41.0)%和(91.6±25.0)%,通过线性拟合求得可卡因ED50值为3.67 mg·kg^(-1)。结论成功建立FR 10可卡因药物辨别模型,可卡因0~10 mg·kg^(-1)诱导的辨别效应呈剂量依赖性增加趋势,ED50值为3.67 mg·kg^(-1)。
AIM To establish the model of cocaine discrimination in rat with a fixed ratio of 10(FR10) and to perform the cocaine discrimination effect and the dose relationship test and 50% effective dose(ED50) value determination. METHODS Thirty-two SD rats were given food training by two experimental procedures: the FR value was gradually increased by 1 and the FR value was automatically increased by 1 every 5 rewards, and rats with successful food training were used to discriminate cocaine 10 mg·kg^(-1) or sodium chloride injection. Subsequently, the SD rats successfully trained were administered with 0, 0.1, 0.5, 1.25, 2.5, 5, 10 mg·kg^(-1) of cocaine for substitution testing and dose-response relationship testing, and the ED50 value was calculated. RESULTS Totally 27 SD rats successfully entered the discrimination training phase after the food training phase. With the program of increasing FR values by 1, 2, 4, 6, and 10, it took(27.2±2.9) days to completed the discrimination training for the first time in 19 SD rats. When cocaine 10 mg·kg^(-1) was substituted with 0, 0.1, 0.5, 1.25, 2.5, 5, 10 mg·kg^(-1) of cocaine in 14 SD rats, the response percentage of cocaine level were(18.7±25.1)%,(2.1±4.0)%,(16.1±37.3)%,(36.4±45.9)%,(57.1±48.8) %,(74.3±41.0)%,(91.1±25.0)%, respectively, and the ED50 value of cocaine was 3.67 mg·kg^(-1) by linear fitting. CONCLUSION The cocaine discrimination model with FR10 was successfully established and the discrimination effect induced by cocaine(0-10 mg·kg^(-1)) showed a dose-dependent increasing trend, with an ED50 value of 3.67 mg·kg^(-1).
作者
张欢
李贝贝
王舒哲
刘小珍
邱云良
陈华英
ZHANG Huan;LI Bei-bei;WANG Shu-zhe;LIU Xiao-zhen;QIU Yun-liang;CHEN Hua-ying(College of Chemistry and Chemical Engineering,Shanghai University of Engineering Science,SHANGHAI 201620,China;Shanghai InnoStar Bio-Tech Co.,Ltd.,China State Institute of Pharmaceutical Industry,SHANGHAI 201203,China;School of Pharmacy,Fudan University,SHANGHAI 201203,China)
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2021年第2期135-139,共5页
Chinese Journal of New Drugs and Clinical Remedies
基金
十三五国家“重大新药创制”科技重大专项(2018ZX09201017-008)
上海市科委研发平台专项(18DZ2290100)。
关键词
可卡因
辨别学习
模型
动物
依赖性评价
cocaine
discrimination learning
models
animal
dependency evaluation
