改良大鼠尼古丁依赖—戒断模型的建立与疼痛敏感性的观察  

ESTABLISHMENT OF MODIFIED RAT MODEL OF NICOTINE DEPENDENCE-WITHDRAWAL AND OBSERVATION OF PAIN SENSITIVITY AFTER NICOTINE WITHDRAWAL

作　　者：刘献文[1] 逯素芬[1,2] 于爱兰[2] 张宗旺[1,2] 

机构地区：[1]徐州医学院江苏省麻醉学重点实验室,徐州221002 [2]山东省聊城市人民医院麻醉科,聊城252000

出　　处：《中国疼痛医学杂志》2013年第11期670-674,共5页Chinese Journal of Pain Medicine

摘　　要：目的:通过皮下注射纯烟碱制作改良大鼠尼古丁依赖-戒断模型,观察尼古丁戒断后大鼠机械刺激缩足阈值(mechanical withdrawal threshold,MWT)和热刺激缩足潜伏期(thermal withdrawal latency,TWL)的变化。方法:SD大鼠30只,采用随机数字表法随机分成5组,每组6只,为正常对照组(C组)、生理盐水组(NS组)、尼古丁3 mg/(kg d)组(NT3组)、尼古丁9 mg/(kg d)组(NT9组)和尼古丁18 mg/(kg d)组(NT18组)。分别给予正常饲养、皮下注射0.9%氯化钠注射液、尼古丁3 mg/(kg d)、尼古丁9 mg/(kg d)和尼古丁18 mg/(kg d),连续7 d,于第7 d末次注射后60 min,皮下注射美加明1 mg/kg。观察大鼠注射尼古丁期间体质量的变化,并分别对美加明激发后的戒断症状进行评分。另外选取C组、NS组和NT9组大鼠,于注射尼古丁7 d后对右下肢足底进行MWT和TWL的测定。结果:(1)注射尼古丁后第7 d,与C组、NS组和NT3组比较,NT9组和NT18组大鼠体重增加明显缓慢(P<0.05);在戒断后第1 d和第2 d,NT9组和NT18组比C组、NS组和NT3组大鼠体重增加明显迅速(P<0.01)。(2)与C组、NS组和NT3组相比,NT9组和NT18组大鼠于美加明激发后表现出明显的戒断症状(P<0.01)。(3)与C组和NS组相比,NT9组大鼠在尼古丁戒断后1 d～7 d足底MWT明显降低,以第1 d、2 d、6 d和7 d尤为显著;TWL亦明显降低,以2 d,3 d,4 d和5 d显著,4 d降至最低。结论:通过连续皮下注射7 d纯烟碱9 mg/(kg d)可以成功制作改良尼古丁依赖—戒断模型。尼古丁戒断后大鼠机械刺激和热刺激疼痛敏感性增高,其具体机制还有待于进一步研究。Objective： To establish a modifed rat model of nicotine dependence-withdrawal by subcutaneous injection of pure nicotine,and to observe changes of mechanical withdrawal threshold（MWT） and thermal withdrawal latency（TWL） in rats after nicotine withdrawal.Methods： Thirty SD rats were randomly divided into 5 groups（6 rats per group）,including the normal control group（Group c）,the normal saline group（NS group）,the nicotine 3 mg/（kg d） group（NT3 group）,the nicotine 9 mg/（kg·d） group（NT9 group）and the nicotine 18 mg/（kg·d） group（NT18 group）.Each group was given normal feeding,subcutaneous injection of normal saline,nicotine 3 mg/（kg·d）,nicotine 9 mg/（kg·d） and nicotine 18 mg/（kg·d） respectively for 7 days.At 60 min after the last injection of nicotine,subcutaneous injection of mecamylamine（1 mg/kg） was administered to each rat.Weight changes of rat during injections of nicotine,and the withdrawal symptom scoring after mecamylamine precipitation was recorded.MWT and TWL were also determined during 7 day injection in the group C,NS group and NT9 group,respectively.Results：（1） On the seventh day after injections of nicotine,compared with C group,NS group and NT3 group,the weight gain of rats in NT9 group and NT18 group signifcantly slowed（P 0.05）; On the frst and second withdrawal days,compared to C group,NS group and NT3 group,the rats in NT9 group and NT18 group obviously had more rapid weight gain（P 0.05 or P 0.01）.（2） Compared with C group,NS group and NT3 group,the rats in NT9 group and NT18 group had signifcant withdrawal symptoms after mecamylamine precipitation（P 0.01）.（3） Compared with the C group and NS group,the rats in NT9 group had signifcantly reduced MWT（especially on the first,second,sixth and seventh days of nicotine withdrawal）,and TWL also signifcantly decreased（especially on the second,third,fourth and ffth withdrawal day）.Conclusion： By continuous subcutaneous injection of pure nicotine at 9 mg/（

关 键 词：尼古丁 美加明 依赖 戒断 疼痛 

分 类 号：R749.6[医药卫生—神经病学与精神病学]