AP-1 DNA-binding activation by methamphetamine involves oxidative stress

Methamphetamine (METH) caused dose‐dependent increases in AP‐1 DNA‐binding activity in both nontransgenic (Non‐Tg) and CuZn‐SOD transgenic (SOD‐Tg) mice. However, the increases in SOD‐Tg mice were less prominent than those observed in Non‐Tg animals. The time‐course of METH‐induced AP‐1 changes was similar in both strains of mice. AP‐1 binding activity showed an initial increase at 1 h, peaked at 3 h, and then gradually declined. AP‐1 binding activity was back to normal by the 72‐h time point. Regional analyses of METH effects revealed increases in the caudate putamen and cerebellum, with the striatum showing relatively higher METH‐induced AP‐1 DNA‐binding activation. These regional effects were also attenuated in the SOD‐Tg mice. These data indicate that METH‐induced stimulation of AP‐1 DNA‐binding depends on cellular redox status. These results are consistent with in vitro studies that have reported that several transcription factors are regulated through redox mechanisms. © 1996 Wiley‐Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.