Alzheimer-like phosphorylation of tau and neurofilament induced by cocaine in vivo.

AIM: To explore the relationship between cocaine-induced cyclin-dependent kinase-5 (CDK5) overexpression or overactivation and Alzheimer-like hyperphosphorylation of cytoskeletal protein. METHODS: Cocaine was injected (ip, 20 mg/kg/d) into rats and the phosphorylation of neuronal cytoskeletal proteins was measured by Western blotting. RESULTS: The levels of phosphorylated tau at PHF-1 epitope and phosphorylated neurofilament determined by SMI31 were elevated in rat brain hippocampus, cortex, and caudatoputamen on d 8 and d 16 after the injection of cocaine, when compared with saline control rat at the same brain regions. On the other hand, the levels of tau non-phosphorylated at tau-1 site and non-phosphorylated neurofilament determined by SMI32 were decreased in same brain regions at the same time points examined. No significant difference of phosphorylated tau and neurofilament at those epitopes was seen on d 4. Although cocaine injection could induce significant hyperphosphorylation of neuronal cytoskeletal proteins, the overexpression of CDK5 and p35 was not detected. CONCLUSION: Peritoneal injection of cocaine induces Alzheimer-like hyperphosphorylation of tau and neurofilament in rat brain, and the effect may be not relevant to an increase in overexpression or overactivation of CDK5.