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Published on: July 29, 2014
The role of mPer1 in morphine dependence in mice
1West China Medical Center, Sichuan University, Chengdu, Sichuan 610041, PR China.
Abstract:
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.
Insights
The mouse mPer1 gene influences morphine dependence development, but not established dependence. DNAzyme targeting mPer1 prevented morphine preference in mice when administered concurrently with the drug.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Circadian clock genes, like period in Drosophila and mPer1/mPer2 in mice, are known to influence responses to drugs such as cocaine.
- The specific role of the mouse mPer1 gene in the development and maintenance of morphine dependence remains largely unexplored.
Purpose of the Study:
- To investigate the role of the mouse mPer1 gene in the development of morphine dependence.
- To determine if mPer1 influences the formation or established state of morphine dependence.
Main Methods:
- Utilized DNAzyme technology to specifically target and inhibit the expression of mPer1 in the central nervous system (CNS) of mice.
- Administered DNAzyme concurrently with morphine or after morphine treatment to assess effects on drug-seeking behavior (place preference).
Main Results:
- DNAzyme treatment successfully attenuated mPer1 expression in the mouse CNS.
- Mice receiving DNAzyme and morphine simultaneously did not develop a place preference for the morphine-associated side.
- Mice treated with DNAzyme after morphine administration exhibited place preference, similar to control groups.
Conclusions:
- The mPer1 gene plays a partial role in the development of morphine dependence.
- mPer1 does not appear to influence morphine dependence once it has been established.
