Induction of the immediate early genes egr-1 and c-fos by methamphetamine in mouse brain

Methamphetamine (METH) is one of the most commonly abused psychostimulant, and is known to induce dopaminergic neurotoxicity by generating oxidative s tress and free radicals. In the present study we investigated the effects o f METH on egr-1 and c-fos immediate early gene induction in different regio ns of mouse brain, at different doses and different time courses. We also m easured the tissue levels of monoamines in order to correlate their changes with gene expression. A single injection of METH (40 mg/kg) significantly increased egr-1 and c-fos mRNA expression within 30 min in frontal cortex, nucleus accumbens, caudate putamen, septum and CAI region of hippocampus. T ime course studies showed that in most cases, both genes were expressed wit hin 30 min and decreased after 60 min. METH produced a significant decrease in striatal dopamine level, reaching a very low level after 24 h. Striatal serotonin level significantly increased and returned to control levels aft er 2 h. These data show that METH induced egr-1 and c-fos mRNA expression i n selective brain areas, which correlated with an alteration in monoamines. (C) 2001 Published by Elsevier Science B.V.