【摘要】 目的研究节律基因Period1在药物精神依赖形成中的作用。方法设计针对节律基因Period1mR NA的核酶 (per1RZ) ,构建以真核表达质粒pcDNA 3.1为基础的per1RZ表达质粒 (pcDNA 3.1 per1RZ) ;体外转录切割实验检测核酶对Period1RNA的切割作用 ;脑室注射pcDNA 3.1 per1RZ ,调节动物节律基因Period1的表达 ;以BALB/C小鼠的吗啡条件性位置偏爱 (CPP)为指标 ,观察pcDNA 3.1 per1RZ对吗啡精神依赖形成的影响。结果体外切割实验发现per1RZ对Period1RNA的切割效率达到60 % ;动物实验证实per1RZ能有效干扰小鼠中枢神经系统Period1基因的表达 ,阻断吗啡条件性位置偏爱的形成。结论节律基因Period1与药物精神依赖的形成有关 ,提示per1RZ可以阻断动物药物精神依赖的形成更多还原

【Abstract】 Objective To investigate the role of circadian gene Period1 on drug dependence. Method The ribozyme cleave the Period1 mRNA(per1RZ) was designed and the per1RZ expression vector(pcDNA 3.1-per1RZ) was constructed based on eukaryotic expression vector pcDNA 3.1. In vitro cleavage experiment proved the target cleave Period1 mRNA ability of per1RZ. Conditional place preference(CPP) paradigm used to investigate the effect of intracerebroventricular (ICV) injection of pcDNA 3.1—per1RZ on drug reward in BALB/C mice. Result Quantitative analysis of in vitro cleavage experiment showed the efficacy of ribozyme per1RZ, about 60% of the Period1 mRNA was cleaved by ribozyme per1RZ. CPP test displayed the block of drug reward in pcDNA 3.1—per1RZ ICV injection group. Period1 expression in brain was attenuated of pcDNA 3.1—per1RZ ICV injection group demonstrated by western blot. Conclusion Interfere the Period1 expression in brain could attenuate the psychological dependence of drug in mammals.更多还原