Liu Y, Wang Y, Wan C, Zhou W, Peng T, Liu Y, Wang Z, Li G, Cornelisson G, Halberg F
West China Medical Center, Sichuan University, Chengdu, Sichuan 610041, PR China.
Neuroscience. 2005;130(2):383-8. doi: 10.1016/j.neuroscience.2004.09.012.
Investigations using Drosophila melanogaster have shown that the circadian clock gene period can influence behavioral responses to cocaine, and the mouse homologues, mPer1 and mPer2, modulate cocaine sensitization and reward. In the present study, we applied DNAzyme targeting mPer1 to interfere the expression of mPer1 in CNS in mice and studied the role of mPer1 on morphine dependence. We found that the DNAzyme could attenuate the expression of mPer1 in CNS in mice. Mice treated with DNAzyme and morphine synchronously did not show preference to the morphine-trained side, whereas the control group did. In contrast, mice treated with DNAzyme after morphine showed preference to the morphine-trained side as well as the control group did. These results indicate that drug dependence seems to be influenced at least partially by mPer1, but mPer1 cannot affect morphine dependence that has been formed.
对黑腹果蝇的研究表明，昼夜节律时钟基因period可影响对可卡因的行为反应，而其小鼠同源基因mPer1和mPer2则可调节可卡因的敏感性和奖赏效应。在本研究中，我们应用靶向mPer1的脱氧核酶干扰小鼠中枢神经系统中mPer1的表达，并研究mPer1在吗啡依赖中的作用。我们发现脱氧核酶可减弱小鼠中枢神经系统中mPer1的表达。同步接受脱氧核酶和吗啡处理的小鼠对吗啡训练侧未表现出偏好，而对照组则表现出偏好。相反，吗啡处理后接受脱氧核酶处理的小鼠与对照组一样，对吗啡训练侧表现出偏好。这些结果表明，药物依赖似乎至少部分受mPer1影响，但mPer1不能影响已形成的吗啡依赖。
