Role of CDK5 in Morphine Dependence-induced Neurofilament Hyperphosphorylation

【Objective】To investigate the changes of cyclin-dependent kinase-5(CDK5)and protein phosphatase-2A(PP-2A),and the effects of them on neurofilament hyperphosphorylation in the cortex of morphine dependence mice.【Methods】Twenty-eight Kunming mice,male and weighing 20-25 g,were randomly divided into control group,morphine dependence group,roscovitine preconditioning group,and vehicle group with 7 mice each.Animals in morphine dependence group,roscovitine preconditioning group,and vehicle group were administered with morphine by subcutaneous injection of morphine 5 mg/kg/d for 6 d.The mice in roscovitine preconditioning group were administered with roscovitine(30 nmoL/mouse)intracerebroventricularly(i.c.v.)30 min before treatment with morphine.The mice in vehicle group were administered with vehicle i.c.v.30 min before treatment with morphine.All the animals were sacrificed to get the prefrontal cortex for detecting the level of neurofilament hyperphosphorylation,p-CDK5(Ser159),and PP-2A with immunoblotting 12 h after the last injections,respectively.【Results】(1)Compared with control group,the level of phosphorylated neurofilament was enhanced,and the level of p-CDK5(Ser159)was increased in morphine dependence group.(2)Compared with vehicle group,the level of phosphorylated neurofilament was reduced,and the level of p-CDK5(Ser159)was decreased in roscovitine preconditioning group.(3)The level of PP-2A was found unaltered in all groups.【Conclusion】Disturbance of cyclin-dependent kinase 5 induced neurofilament hyperphosphorylation in morphine dependence mice brain.