薄荷精油对尼古丁戒断大鼠焦虑行为的治疗作用及其机制

Therapeutic effect of peppermint essential oil on nicotine-withdrawal induced anxiety-like behavior in rats and its relevant mechanism

目的探讨薄荷精油对尼古丁戒断大鼠焦虑行为的作用及机制。方法选取40只成年雄性Sprague-Dawley大鼠,随机平均分为生理盐水对照组、尼古丁戒断模型组、薄荷精油(PEO)低浓度干预组、PEO高浓度干预组和PEO高浓度对照组5组。给模型组和薄荷精油干预组皮下注射尼古丁(每次0.4 mg/kg,2次/天)共7天,然后尼古丁戒断3天制备尼古丁戒断焦虑行为模型;剩下两组注射等容积生理盐水。在3天的戒断时间里,精油组大鼠分别吸入薄荷精油每天1次,每次吸入30 min。在第3天精油干预1 h后,大鼠先后在旷场和高架十字迷宫测试大鼠焦虑行为。随后利用酶联免疫吸附剂测定法(ELISA)测定血液的皮质酮浓度,利用高效液相色谱法检测大脑终纹床核(BNST)的去甲肾上腺素(NE)浓度。结果在行为学检测中,尼古丁戒断大鼠表现出明显的焦虑行为,即在旷场中央区的活动路程和时间明显减少,差异均有统计学意义(P<0.05);在高架十字迷宫开臂进入次数及滞留时间百分比降低,差异均有统计学意义(P<0.05)。但PEO低浓度和高浓度干预分别改善这些焦虑行为学指标.差异均有统计学意义(P<0.05)。ELISA结果显示,尼古丁戒断大鼠血浆中皮质酮浓度明显升高,而薄荷精油干预治疗可抑制此升高,差异均有统计学意义(P<0.05)。同时,高效液相检测发现,尼古丁戒断导致大鼠BNST的NE浓度增高,而薄荷精油干预也可抑制NE浓度增高,差异均有统计学意义(P<0.05)。结论薄荷精油吸入可通过抑制尼古丁戒断所致大鼠BNST的NE浓度升高,改善血液中皮质酮水平,继而治疗尼古丁戒断大鼠焦虑行为。

Objective To evaluate the therapeutic effect of peppermint essential oil(PEO)on nicotine withdrawal-induced anxiety and investigate the relevant mechanisms.Methods Forty adult male Sprague-Dawley(SD)rats were randomly assigned to five experimental groups,saline-treated control group,nicotine withdrawal model group,low-dose PEO intervention group,high dose PEO treatment group,and high-dose PEO control group.To induce nicotine withdrawal anxiety behavior model,rats received subcutaneous administration of nicotine(0.4 mg/kg)twice a day for 7 consecutive days,followed by 3 days withdrawal.During the withdrawal period,the rats were treated with PEO(or tap water)once a day for 30 minute.One hour after the third PEO,the rats were sequentially participated in the open field(OF)test and the elevated plus maze(EPM)test,and then the concentration of corticosterone in blood was determined by enzyme linked immunosorbent assay(ELISA),and the concentration of norepinephrine(NE)in the brain terminal bed nucleus(BNST)was determined by high performance liquid chromatography(HPLC).Results In the behavioral test,the nicotine withdrawn rats displayed anxiety indexed by the decreased stay time and the shortened travel distance in the central area of the OF,the differences were statistically significant(P<0.05).The visiting frequency to and percentage of exploring time in the open arms of the EPM reduced,the differences were statistically significant(P<0.05).However,all these anxiety indices were respectively attenuated by both low-dose and high-dose PEO intervention,the differences were statistically significant(P<0.05).ELISA assay discovered nicotine withdrawal elevated the plasma corticosterone level,which was inhibited by PEO,the differences were statistically significant(P<0.05).High performance liquid chromatography analysis revealed,the norepinephrine level in the BNST of nicotine withdrawn rats was enhanced that was also blocked by PEO,the differences were statistically significant(P<0.05).Conclusions Peppermint essential oil inhalation could inhibit the increase of NE concentration of BNST induced by nicotine withdrawal in rats,improve the level of corticosterone in blood,and then treat the anxiety behavior of nicotine withdrawal rats.