烟草添加剂薄荷醇和桉叶素影响尼古丁依赖的动物实验研究

Animal Experimental Study of the Role of Menthol and Cineole,Two Tobacco Additives,on Nicotine Dependence

目的建立大鼠尼古丁静脉自身给药模型,并用该模型探索两种芳香添加剂——薄荷醇和桉叶素对尼古丁依赖性的影响。方法纳入30只雄性SD(Sprague-Dawley)大鼠,行颈静脉插管术后进行尼古丁固定浓度自身给药训练以建立大鼠尼古丁自身给药模型;建模成功后,将所有大鼠随机分成3组分别经腹腔注射薄荷醇、桉叶素、二甲基亚砜(溶剂对照),分别采用固定比率程序(fixed-ratio schedule,FR),即FR1(大鼠每进行1次有效鼻触,得到1次尼古丁注射)、FR2(大鼠每进行2次有效鼻触,得到1次尼古丁注射)、FR5(大鼠每进行5次有效鼻触,得到1次尼古丁注射)测试获得不同程序下大鼠有效鼻触反应数、无效鼻触反应数及尼古丁注射针数。结果经尼古丁自身给药训练10 d后,30只大鼠有效鼻触反应数和注射针数明显升高并稳定在较高水平,有效鼻触反应数高于无效鼻触反应数(P<0.001),成功建立大鼠尼古丁静脉自身给药模型。测试阶段,FR2程序下,薄荷醇组有效鼻触反应数降低(P=0.020),FR5程序下,组别与时间水平的有效鼻触反应数指标存在明显交互作用(P<0.001),薄荷醇组有效鼻触数在第3天降低(P=0.011),桉叶素组则在第3天升高(P=0.003),溶剂对照组无明显变化。结论薄荷醇及桉叶素均对尼古丁依赖有影响,在尼古丁较难获取时,薄荷醇抑制尼古丁依赖性,桉叶素则增加尼古丁依赖性。

Objective To establish a nicotine intravenous self-administration rat model,and to examine,with this model,the effects of two flavoring additives,menthol and cineole,on nicotine dependence.Methods Thirty male Sprague-Dawley(SD)rats were included in the study.After jugular venous catheterization was performed,fixed concentration of nicotine was administered in order to train the rats and establish the rat model of intravenous selfadministration groups,receiving intraperitoneal injection of menthol,cineole,and dimethyl sulfoxide(DMSO),the vehicle that was used for the control group.The rats were tested with different fixed-ratio(FR)schedules,including FR1 schedule,in which the rat received one nicotine infusion for every active nose poke,FR2 schedule,in which the rat received one nicotine infusion for every two active nose pokes,and FR5 schedule,in which the rat received one nicotine infusion for every five active nose pokes.The number of active and inactive poke responses and the number of nicotine infusion were documented accordingly.Results After 10 days of training in nicotine self-administration,the 30 rats demonstrated significant increase in the number of active poke responses and the number of nicotine infusion,which were maintained at a stable and relatively high level.The number of active poke responses was significantly higher that of inactive poke responses(P<0.001).The rat model of intravenous nicotine self-administration was successfully established.In the testing phase,under the FR2 schedule,the menthol group showed a reduced number of active poke responses(P=0.020).Under the FR5 schedule,the groups showed obvious interaction between time and the number of active poke responses(P<0.011),with the menthol group showing reduced number of active poke responses on day three(P=0.011)and the cineole group showing rising number of active poke responses on day three(P=0.003).The DMSO control group did not show any significant change.Conclusions Menthol and cineole are shown to have an effect on nicotine dependence.When there is relative difficulty involved in obtaining nicotine,menthol suppresses nicotine dependence,whereas cineole enhances nicotine dependence.