延胡索甲素与左旋延胡索乙素抗吗啡躯体依赖和精神依赖的作用研究

Effect of corydalis monomers against morphine physical dependence and physical dependence

目的观察并比较延胡索甲素(corydaline,Cor)与左旋延胡索乙素(l-tetrahydropalmatine,l-THP)抗吗啡躯体依赖和精神依赖的作用。方法 SD大鼠随机分为对照组、模型组、Cor组、l-THP组。连续递增sc吗啡9 d后,纳洛酮促瘾,制备吗啡依赖大鼠催促戒断模型,促瘾前30 min ip Cor(40、80 mg/kg)或l-THP(5.0、10.0 mg/kg),观察大鼠戒断症状和体质量的降低;应用旷场实验,观察Cor(5、10 mg/kg)和l-THP(2.5、5.0 mg/kg)对吗啡诱导的大鼠自发活动的影响、对吗啡连续递增给药致大鼠行为敏化效应的影响,以及Cor(10、20、40 mg/kg)和l-THP(2.5、5.0、10.0 mg/kg)对大鼠自发活动的影响。结果 Cor(40、80 mg/kg)、l-THP(5.0 mg/kg)对吗啡催促戒断症状无显著改善作用,10 mg/kg l-THP显著改善大鼠戒断症状(P<0.05);Cor和l-THP对吗啡降低大鼠体质量效应有改善趋势,但差异不显著;Cor 40 mg/kg以下剂量、l-THP 10 mg/kg以下剂量对大鼠自发活动无显著影响;Cor(5、10 mg/kg)和l-THP(2.5、5.0 mg/kg)均可显著降低吗啡诱发的大鼠高活动性行为、行为敏化的形成(P<0.05、0.01)。结论 Cor和l-THP对吗啡所致的大鼠躯体依赖和精神依赖均有不同程度的调节作用,l-THP的起效剂量明显低于Cor。

Objective To observe and compare the effect of corydaline （Cor） and 1-tetrahydropalmatine （1-THP） against morphine physical dependence and physical dependence. Methods SD rats were randomly divided into control group, model group, Cor group, and 1-THP group. After 9 d of sc administration of morphine by dose escalation, ip administration of naloxone to establish animal models of precipitated withdrawal in morphine-dependent rats. Rats were ip injected with Cor （40 and 80 mg/kg） or 1-THP （5 and 10 mg/kg） 30 min before administration of naloxone. And then, the withdrawal symptoms and body weight change of rats were observed. Using open-field test, the effect of Cor （5 and 10 mg/kg） and 1-THP （2.5 and 5 mg/kg） pretreatment on spontaneous activities induced by acute morphine and behavioral sensitization induced by increasing dosages of morphine, and the effect of Cor （10, 20, and 40 mg/kg） and 1-THP （2.5, 5, and 10 mg/kg） on spontaneous activities were observed. Results Cor （40 and 80 mg/kg） and I-THP （5 mg/kg） had no significant decrease on symptoms of precipitated morphine withdrawal, but 1-THP （10 mg/kg） could significantly decrease withdrawal symptoms in rats （P 〈 0.05）. Cor and 1-THP could reversed the trend of the weight loss induced by naloxone-precipitated morphine withdrawal in rats, but there was no significant difference. Cor with doses less than 40mg/kg and I-THP with doses lower than 10mg/kg could have no effect on locomotion activity in rats. Cor （5 and 10 mg/kg） and 1-THP （2.5 and 5 mg/kg） significantly reduced morphine-induced high activity in rats and the fomation of behavioral sensitization （P 〈 0.05, 0.01）. Conclusion Cor and 1-THP have varying degrees of therapeutic effects on morphine physical dependence and psychic dependence, and 1-THP has more prospects by the lower onset dose than Cor.