Ribozyme attenuates reward to morphine in mice by interfering with mper1 gene expression

Abstract

Studies on Drosophila melanogaster have shown that the period gene, a circadian clock gene and essential component of the underlying molecular feedback loop, can influence behavioural responses to cocaine. The mouse homologues, mPer1 and mPer2, were also shown to modulate cocaine sensitization and reward. Reportedly, normal expression of the per gene is important for the development of cocaine sensitization in Drosophila and in the mouse. This study examines the role of mPer1 on morphine addiction by applying a ribozyme to interfere with the expression of mPer1 in the central nervous system of mice. A plasmid based on pcDNA3.1 was constructed, using the expression of a hammerhead ribozyme that can selectively cleave the mPer1 mRNA. The ribozyme's presence was associated with a statistically significant reduction in mPer1 mRNA. Mice treated with the ribozyme and morphine synchronously did not show any preference for the morphine-paired side, whereas the control mice did. These results suggest that mPer1 is involved in the reward formation to morphine.

Keywords:

• Circadian
• CPP
• drug addiction
• morphine
• mPer1
• ribozyme

Acknowledgments

This study was supported by the National Nature Science Foundation of China (No. 39970275; No. 30070288 to Z. Wang; No. 30070198 to C. Wan), US Public Health Service (GM-13981 to F. Halberg), and Dr. h.c. Earl Bakken Fund (to G. Cornélissen and F. Halberg).