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.