Phosphorylation of tau and neuroflament in prefrontal cortex of rat brain after acute and chronic morphine administration

AIM: To investigate the phosphorylation of cytoskeletal protein in the rat brain after acute and chronic morphine administration,and to determine the relationship between morphine-induced cyclin-dependent kinase-5 ( CDK5) over-expression and herphosphorylation of cytoskeletal protein. METHODS: Forty male SD rats,weighing 220-250 g,were randomly divided into acute control group,acute morphine administration group,chronic control group and chronic morphine administration group ( 10 rats in each group) . The rats in acute morphine administration group received intraperitoneal injection of morphine at dose of 30 mg/kg. The rats in chronic morphine administration group were injected with morphine intraperitoneally twice a day ( 10 mg/kg at time 8: 00 and 22: 00,respectively) for 10 days. The rats in acute control group and chronic control group received equi-volume of normal saline in the same way. Two hours after the last injections,the rats were sacrificed and the prefrontal cortex was collected for detecting the phosphorylation levels of neuronal cytoskeletal proteins,CDK5 and p35 by the method of immunoblotting. RESULTS: ( 1) In acute morphine administration group,the level of phosphorylated tau at the sites of Thr205,Ser404 and phosphorylated neurofilament was increased. The level of CDK5 was also increased. ( 2) In chronic morphine administration group,the levels of phosphorylated tau and phosphorylated neurofilament were enhanced,but the level of CDK5 was not changed markedly. ( 3) Compared to acute morphine administration group,the levels of phosphorylated tau and phosphorylated neurofilament were decreased in chronic morphine administration group. ( 4) The level of p35 was unchanged in all groups. CONCLUSION:Acute or chronic morphine administration induces hyperphosphorylation of tau and neurofilament in the rat cortex,and the changes may be not relevant to over-expression of CDK5.