目的 觀察并比較延胡索甲素(corydaline,Cor)與左旋延胡索乙素(l-tetrahydropalmatine,l-THP)抗嗎啡軀體依賴和精神依賴的作用。方法 SD大鼠隨機(jī)分為對照組、模型組、Cor組、l-THP組。連續(xù)遞增sc嗎啡9 d后,納洛酮促癮,制備嗎啡依賴大鼠催促戒斷模型,促癮前30 min ip Cor(40、80 mg/kg)或l-THP(5.0、10.0 mg/kg),觀察大鼠戒斷癥狀和體質(zhì)量的降低;應(yīng)用曠場實(shí)驗(yàn),觀察Cor(5、10 mg/kg)和l-THP(2.5、5.0 mg/kg)對嗎啡誘導(dǎo)的大鼠自發(fā)活動的影響、對嗎啡連續(xù)遞增給藥致大鼠行為敏化效應(yīng)的影響,以及Cor(10、20、40 mg/kg)和l-THP(2.5、5.0、10.0 mg/kg)對大鼠自發(fā)活動的影響。結(jié)果 Cor(40、80 mg/kg)、l-THP(5.0 mg/kg)對嗎啡催促戒斷癥狀無顯著改善作用,10 mg/kg l-THP顯著改善大鼠戒斷癥狀(P<0.05);Cor和l-THP對嗎啡降低大鼠體質(zhì)量效應(yīng)有改善趨勢,但差異不顯著;Cor 40 mg/kg以下劑量、l-THP 10 mg/kg以下劑量對大鼠自發(fā)活動無顯著影響;Cor(5、10 mg/kg)和l-THP(2.5、5.0 mg/kg)均可顯著降低嗎啡誘發(fā)的大鼠高活動性行為、行為敏化的形成(P<0.05、0.01)。結(jié)論 Cor和l-THP對嗎啡所致的大鼠軀體依賴和精神依賴均有不同程度的調(diào)節(jié)作用,l-THP的起效劑量明顯低于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.

重大新藥創(chuàng)制科技重大專項(xiàng)(2013ZX09302303);重大新藥創(chuàng)制科技重大專項(xiàng)(2012ZX09301003-001-008);北京市科委基金項(xiàng)目(Z131100006513010)