侧脑室注射Conantokin-G类似物拮抗吗啡诱导小鼠奖赏效应的研究

EFFECTS OF CONANTOKIN-G ANALOGUE INJECTION INTO LATERAL VENTRICLE ON MORPHINE-INDUCED REWARDING IN MICE

目的:探究Glu-Con-G、Glu-Con-G[1-11]和Glu-Con-G[S16Y]抗吗啡精神依赖的药效,为进一步设计、筛选抗吗啡依赖的芋螺毒素类似物提供理论和实验依据。方法:采用清洁级♂昆明种小鼠,用条件性位置偏爱(conditioned place preference,CPP)模型检测侧脑室给予3种芋螺毒素类似物对小鼠吗啡精神依赖效应及行为学的影响。结果:120、240、480、960 pmol Glu-Con-G,120、240、480 pmol Glu-Con-G[1-11]和480、960 pmol Glu-Con-G[S16Y]对吗啡诱导小鼠CPP的表达和复燃有抑制作用,且在最高受试剂量时均不影响小鼠的运动活性及探索行为。结论:Glu-Con-G、Glu-Con-G[1-11]、Glu-Con-G[S16Y]可拮抗吗啡诱导小鼠CPP的表达和复燃,具有抗吗啡依赖作用,且不影响其运动活性和探索行为,有望成为抗吗啡依赖的潜在药物。

Objective：To analyze the effects of Glu-Con-G、Glu-Con-G and Glu-Con-G on morphine dependence,providing a direction to design the structure of Conantokin-G analogues.Methods：Male Kunming mice（18-20 g） were used in this experiment.Conditioned place preference model was used for assessing the effects of Glu-Con-G、Glu-Con-G and Glu-Con-G on morphine dependence.Results：Glu-Con-G（120,240,480,960 pmol）,Glu-Con-G（120,240,480 pmol） and Glu-Con-G（480,960 pmol）inhibited the expression and reinstatement of morphine-induced CPP by single intracerebroventricular administration,with no significant behavioral disorders under the experimental conditions.Conclusion：These results indicate that three Conantokin-G analogues can inhibit morphine dependence.They are expected to become potential anti-addictive drugs.