不同给药时间间隔对吗啡诱导小鼠条件性位置偏爱模型的影响  

Effect of Intervals of Drug Administration on Morphine-induced Conditioned Place Preference Models in Mice

作　　者：熊剑 油珅 长孙东亭[1] 李晓丹[1] 罗素兰[1] XIONG Jian;YOU Shen;ZHANGSUN Dongting;LI Xiaodan;LUO Sulan(Key Laboratory of Tropical Biological Resources,Ministry of Education,Haikou Key Lab for Marine Drugs,Hainan University,Haikou,Hainan 570228,China)

机构地区：[1]海南大学热带生物资源教育部重点实验室/海口市海洋药物重点实验室,海口570228

出　　处：《热带生物学报》2021年第3期363-368,共6页Journal of Tropical Biology

基　　金：国家自然科学基金项目(41966003),海南省自然科学基金项目(219QN150)。

摘　　要：为比较不同给药时间间隔下,同等剂量的吗啡诱导条件性位置偏爱(CPP)模型的差异,为后续抗吗啡依赖药物的筛选奠定基础,本研究建立了不同时间间隔的吗啡诱导CPP模型,(1)吗啡组(24 h):连续4 d皮下注射,上午注射吗啡(5 mg·kg^(−1)),下午注射生理盐水,吗啡给药间隔24 h,建立CPP模型;(2)吗啡组(48 h):连续8 d皮下注射,1、3、5、7 d注射吗啡(5 mg·kg^(−1)),2、4、6、8 d注射生理盐水,吗啡给药间隔48 h,建立CPP模型。测定造模前后小鼠在伴药箱的停留时间\造模后CPP得分及CPP模型维持时间。结果表明,吗啡给药时间间隔24 h和48 h均能显著增加小鼠在伴药箱内的停留时间,造模后CPP得分明显增加,吗啡组(24 h)小鼠CPP模型能持续5 d,而吗啡组(48 h)小鼠CPP模型能持续15 d。短期内给药时间间隔不影响CPP模型的形成,与吗啡组(24 h)进行长期对比,给药时间间隔为48 h时,CPP模型维持时间更长、不易消退。To compare the difference of the morphine-induced conditioned place preference(CPP)models with the same dose of morphine under different time intervals of drug administration,morphine morphine-induced CPP models were established to provide a reference for screening anti-morphine addiction drug.Morphine groups(24 s)and(48 h)and saline groups(24 h)and(48 h)were designed in this experiment.The morphine group(24 h)received a subcutaneous injection for 4 consecutive days,and the mice were injected with morphine at the dose of 5 mg·kg^(−1) in the morning,and with saline in the afternoon.The interval of morphine administration in this group was 24 hours.In the morphine group(48 h)subcutaneous injections were given to mice for 8 consecutive days,and the mice were injected with morphine at 5 mg·kg^(−1) at days 1,3,5 and 7,and with saline at days 2,4,6 and 8.Morphine was administered at an interval of 48 hours in this group.The saline groups(24 h)and(48 h)were given subcutaneous injection but only with saline.CPP models for the morphine groups were then established.The time spent in drug-paired compartments was recorded to explore the establishment and maintenance of the CPP models for the morphine groups,and CPP scores were also calculated.The results showed that morphine significantly increased the time spent in the drug-paired compartments and the CPP scores when administered to the mice at respective intervals of 24 hours and 48 hours.The mouse CPP model of the mice lasted for 5 days in the morphine group(24 h)and for 15 days in the morphine group(48 h).It is concluded that the time interval of drug administration did not affect the establishment of the CPP model in a short term and that the mouse CPP model lasted longer with a delay in the extinction of the mouse CPP in the morphine group(48 h)than in the morphine group(24 h)in a long term.

关 键 词：给药时间间隔 吗啡 小鼠条件性位置偏爱模型 维持时间 

分 类 号：R969.3[医药卫生—药理学]