大麻二酚对甲基苯丙胺诱导小鼠行为敏化及条件性位置偏爱的影响

Effect of cannabidiol on behavioral sensitization and conditioned place preference induced by methamphetamine in mice

目的 研究大麻二酚(CBD)在甲基苯丙胺(METH)成瘾中的对抗作用。方法 以雄性C57BL/6J小鼠为研究对象,采用小鼠行为敏化实验,分别观察形成期伴随ip给予或激发期单次ip给予CBD 20,40和80 mg·kg^(-1)后小鼠运动距离,评价CBD对行为敏化形成或点燃的影响;采用小鼠条件性位置偏爱(CPP)实验,分别观察形成期伴随ip给予、表达期测试前单次ip给予或消退期伴随多次ip给予CBD 20,40和80 mg·kg^(-1)后小鼠CPP得分,评价CBD对CPP形成、表达和重建的影响。结果 在行为敏化实验中,CBD 40和80 mg·kg^(-1)显著抑制METH诱导行为敏化的形成或点燃(P<0.05)。CPP实验中,CBD各剂量对CPP形成和表达均无显著对抗作用,但CBD 80 mg·kg^(-1)显著抑制METH诱导CPP重建(P<0.05)。结论 CBD对METH的急性效应无明显对抗作用,但显著抑制METH诱导的动机敏化,并干预成瘾记忆的消退学习过程,从而降低成瘾行为重建。

OBJECTIVE To study the antagonistic effect of cannabidiol (CBD) on methamphetamine (METH) addiction.METHODS With male C57BL/6J mice as the subjects,the behavioral sensitization experiment of mice was used to observe the movement distance of mice after a single ip administration of CBD 20,40 and 80 mg·kg^(-1)in the formation stage or in the challenge stage,and to evaluate the effect of CBD on the formation or priming of behavioral sensitization.The CPP scores of mice were observed in the conditioned place preference (CPP) experiment,and the effects of CBD on the formation,expression or reactivation of CPP were evaluated by observing the CPP scores of mice after the formation stage accompanied by ip administration,the single ip administration before the expression stage test,or the extinction stage accompanied by multiple ip administration of CBD 20,40 and 80 mg·kg^(-1).RESULTS In behavioral sensitization experiments,CBD 40 and 80 mg·kg^(-1)significantly inhibited the development or priming of METH-induced behavioral sensitization (P<0.05).In the CPP experiment,CBD 20,40 and 80 mg·kg^(-1)did not significantly counteract the development and expression of CPP,but CBD 80 mg·kg^(-1)significantly inhibited the reactivation of CPP induced by METH (0.5 mg·kg^(-1))(P<0.05).CONCLUSION CBD does not significantly counteract the acute effects of METH,but can significantly inhibit METH-induced motivational sensitization and intervene in the extinction learning process of addictive memory,thereby reducing the reactivation of addictive behavior.