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 l-tetrahydropalmatine (l-THP) against morphine physical dependence and physical dependence. Methods SD rats were randomly divided into control group, model group, Cor group, and l-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 l-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 l-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 l-THP (2.5, 5, and 10 mg/kg) on spontaneous activities were observed. Results Cor (40 and 80 mg/kg) and l-THP (5 mg/kg) had no significant decrease on symptoms of precipitated morphine withdrawal, but l-THP (10 mg/kg) could significantly decrease withdrawal symptoms in rats (P < 0.05). Cor and l-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 l-THP with doses lower than 10mg/kg could have no effect on locomotion activity in rats. Cor (5 and 10 mg/kg) and l-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 l-THP have varying degrees of therapeutic effects on morphine physical dependence and psychic dependence, and l-THP has more prospects by the lower onset dose than Cor.

重大新药创制科技重大专项(2013ZX09302303);重大新药创制科技重大专项(2012ZX09301003-001-008);北京市科委基金项目(Z131100006513010)