Studies with MEK inhibitors indicate that several drugs of abuse regulate the activity of transcription factors and increase gene expression through ERK-dependent mechanisms. For example, cocaine increases c-fos mRNA and phosphorylation of Elk-1, and these effects are inhibited by the MEK inhibitor SL327.16 SL327 also inhibits increases in c-fos and egr-2 mRNA induced by methamphetamine,35 and increases in proenkephalin and preprodynorphin mRNA induced by amphetamine.20 THC increases Elk-1 phosphorylation and levels of zif268 mRNA levels, and these increases are inhibited by SL327 as well.32
