芋螺毒素类似物静脉给药抑制小鼠吗啡依赖作用研究

目的:探究尾静脉给予芋螺毒素类似物Glu-Con-G、Glu-Con-G1-11]和Glu-Con-G1-13]对小鼠吗啡依赖的影响,验证静脉给药的可行性。方法:建立条件性位置偏爱(conditioned place preference,CPP)模型,观察静脉给予3种芋螺毒素类似物对小鼠吗啡依赖的作用。结果:(1)50、100、200μg.kg-1 Glu-Con-G、Glu-Con-G1-11]和Glu-Con-G1-13]对吗啡成瘾小鼠CPP表达有抑制作用;(2)100、200μg.kg-1Glu-Con-G及50、100、200μg.kg-1 Glu-Con-G1-11]、Glu-Con-G1-13]对吗啡成瘾小鼠CPP复燃有拮抗作用;(3)200μg.kg-1Glu-Con-G、Glu-Con-G1-11]和Glu-Con-G1-13]均不影响小鼠的运动活性及探索行为。结论:静脉给予3种芋螺毒素类似物对吗啡诱导的CPP表达、复燃均具有抑制作用;Glu-Con-G1-11]抗吗啡依赖的作用优于Glu-Con-G,且分子量小于Glu-Con-G1-13],有望成为一种潜在的抗成瘾药物。

INHIBITORY EFFECT OF CONOTOXIN ANALOGUES TREATED INTRAVENOUSLY ON MORPHINE DEPENDENCE IN MICE

Objective: To investigated the role of intravenous conotoxin analogues on morphine dependence in mice.Furthermore,feasibility of intravenous administration of conotoxin analogues was also verified.Methods: Male Kunming mice(18-20g) were used in this experiment.Conditioned place preference(CPP) model was used as parameters for assessing the effect of intravenous injection Glu Con-G,Glu-Con-G1-11] and Glu-Con-G1-13] on morphine dependence.Results: Glu Con-G,Glu-Con-G1-11] and Glu-Con-G1-13](50,100,200 μg.kg-1) by intravenous administration attenuated the expression of morphine-induced CPP(P < 0.05);Glu-Con-G(100,200 μg.kg-1) and Glu-Con-G1-11],Glu-Con-G1-13](50,100,200 μg·kg-1) suppressed the reinstatement of morphine-induced CPP(P < 0.05);All the conotoxin analogues(200 μg·kg-1) induced no significant behavioral disorder under the experimental conditions(P > 0.05).Conclusion: These results indicate that three conotoxin analogues can inhibit dependence induced by morphine.Glu Con-G1-11]is expected to become a potential anti-addictive drug as its better effect than Glu Con-G on inhibiting morphine dependence,and smaller molecular weight than Glu-Con-G1-13].