Inhibition of Period1 gene attenuates the morphine-induced ERK-CREB activation in frontal cortex, hippocampus, and striatum in mice.
OBJECTIVE
Recent studies demonstrated that the Period1 gene (Per1) is involved in behavioral alterations induced by addictive drugs. We explored the effects of inhibiting expression in brain of Per1 on morphine conditioned place preference (CPP) and morphine-induced phosphorylation of extracellular signal-regulated kinase (ERK) and cAMP-response element binding protein (CREB) in mice.


METHODS
During the first three sessions of conditioning, the male mice were intracerebroventricularlly (i.c.v.) injected with vehicle or deoxyribozyme 164 (DRz164) which cleaves per1 mRNA before subcutaneous (s.c.) injection morphine. The control group was given i.c.v. injection vehicle and s.c. injection saline instead of morphine. After testing CPP, mice were sacrificed and phosphorylated ERK and CREB in the frontal cortex, hippocampus, and striatum were examined by immunohistochemistry.


RESULTS
Mice pretreated with DRz164 did not acquire morphine CPP. Pretreatment with DRz164 significant attenuated the morphine-induced activation of ERK and CREB in the frontal cortex, hippocampus, and striatum.


CONCLUSIONS
Our results indicated that per1 plays an important role in morphine reward, and ERK-CREB pathway was involved in the effects of per1. We suggested that per1 gene may be a potential treatment target for drug addition.
Key Laboratory of Chronobiology of Health Ministry, Basic and Forensic School, Sichuan University, Chengdu, China. lisuxia70@163.com
Su-Xia
SX
Li
Zheng-Rong
ZR
Wang
Jing
J
Li
Zu-Gui
ZG
Peng
Wei
W
Zhou
Mei
M
Zhou
Lin
L
Lu
D000818:Animals; D018797:Cell Cycle Proteins / Q000187:drug effects* / Q000235:genetics; D003216:Conditioning, Operant / Q000187:drug effects; D003342:Corpus Striatum / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects* / Q000378:metabolism; D021881:DNA, Catalytic / Q000494:pharmacology; D016503:Drug Delivery Systems; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects* / Q000378:metabolism; D005625:Frontal Lobe / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000188:drug therapy / Q000503:physiopathology; D009687:Nuclear Proteins / Q000187:drug effects* / Q000235:genetics; D056950:Period Circadian Proteins; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D012201:Reward
D018797:Cell Cycle Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D021881:DNA, Catalytic; D009687:Nuclear Proteins; C539023:Per1 protein, mouse; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D009020:Morphine; D048049:Extracellular Signal-Regulated MAP Kinases