The extracellular signal-regulated kinase signaling pathway is involved in the modulation of morphine-induced reward by mPer1.
Although there are clear interactions between circadian rhythms and drug addiction, mechanisms for such interactions remain unknown. Studies have shown that the circadian clock gene Period in Drosophila melanogaster could 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 its effects on morphine-induced reward and its molecular mechanism. The results demonstrated that the DNAzyme could attenuate the expression of mPer1 in CNS in mice and downregulate the increased extracellular signal-regulated kinase (ERK) activity induced by morphine in whole brain and the nucleus accumbens, the key region of drug addiction. Mice treated with morphine and injected intracerebroventricularly with DNAzyme did not show preference to the morphine-trained side. These results indicate that drug dependence seems to be influenced at least partially by mPer1 and its mechanism may involve the ERK signal pathway.
Liu
Y
Y
Health Ministry Key Lab of Chronobiology, West China Medical Center, Sichuan University, Chengdu, Sichuan 610041, PR China.
Wang
Y
Y
Jiang
Z
Z
Wan
C
C
Zhou
W
W
Wang
Z
Z
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000502:physiology*; D003216:Conditioning, Operant / Q000187:drug effects; D021881:DNA, Catalytic / Q000494:pharmacology; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000502:physiology*; D056950:Period Circadian Proteins; D012201:Reward; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D018797:Cell Cycle Proteins; D021881:DNA, Catalytic; D004791:Enzyme Inhibitors; D009294:Narcotics; D009687:Nuclear Proteins; C539023:Per1 protein, mouse; D056950:Period Circadian Proteins; D009020:Morphine; D048049:Extracellular Signal-Regulated MAP Kinases