Methamphetamine-induced increase in striatal p53 DNA-binding activity is attenuated in Cu,Zn-superoxide dismutase transgenic mice.

The striatal DNA-binding activities of p53 as a transcription factor were gradually increased at several days after a single methamphetamine (METH) injection, while they were more rapidly increased within several hours after repeated METH injections (x4 with a 2 h interval). The elevation of striatal p53 DNA-binding after repeated METH injections was markedly attenuated in Cu,Zn-superoxide dismutase transgenic mice, but not affected by treatments with N-methyl-D-aspartate or D1 receptor antagonists. The present results suggest that METH-induced production of reactive oxygen species activates striatal p53 DNA-binding activity; this, in turn, may activate other downstream pathways that are responsible for chronic neurotoxicity of METH.