The Effects Of Circadian System On Morphine Dependence And Learning And Memory

Objectives:The effects of circadian system on drug dependence and cognition, including the role of mPer1 on morphine dependence and the relationship between different light/dark cycle and learning and memory, were investigated in the present article.Methods:Experiment 1: The role of mPer1 on morphine dependence in mice. Male BALB/C mice were used in the research. DNAzyme, known as the "10-23" model, targeting mPer1 was designed and synthesised. Mice treated with DNAzyme and morphine synchronously and mice treated with DNAzyme after morphine, controlled with inactive oligonucleotide, were researched. Conditional position preference (CPP) and the western blot were used to measure the rewarding properties of morphine dependence and immunoactivity of mPER1 in the whole brain, respectively. The efficacy of the DNAzyme targeting mPer1 to cleave the substrate of mPer1 mRNA prepared an in vitro transcript was tested in vitro.Experiment 2: Period length of the light/dark cycle influences the learning and memory in mice. Male ICR mice under controlledenvironment were given artificial light of different LD cycle including LD5/5 group (light: 5h; dark: 5h), LD12/12 group (light: 12h; dark: 12h) and LD22/22 group (light: 22h; dark: 22h). The mice were raised for 6 weeks. The parameters including motor activity, the plasma corticosterone concentrations by radio-immunity assay and learning and memory by Morris water maze were detected.Results:Experiment 1: DNAzyme could not only cleave mPer1 mRNA in vitro, but also interfere with expression of mPer1 in vivo. The immunoactivity of mPer1 in whole brain of mice treated with DNAzyme was attenuated and the circadian pattern of mPer1 was also influenced. According to CPP, mice treated with DNAzyme and morphine synchronously did not show preference to morphine-trained side, whereas mice treated with DNAzyme after morphine did.Experiment 2: The rhythms of locomotor activity and the plasma corticosterone concentration of mice under LD12/12 were consistent with the LD cycle. The locomotor activity, plasma corticosterone concentrations and ability of leaning and memory of mice under LD5/5 and LD22/22 were higher than that of mice under LD12/12. The enhanced ability of learning and memory may be related to the high concentrations of plasma corticosterone.Conclusion:This study demonstrated that DNAzyme targeting to mPer1 could cleavemPer1 mRNA in vitro, attenuate the expression of mPer1 in vivo, and interfere with the rhythm of mPer1 in whole brain of mice. 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.The rhythm of locomotor activity was consistent with LD cycle. Different LD cycle had different effect on plasma corticosterone concentrations and ability of learning and memory.