In summary, we have demonstrated regulation of electron transport gene expression in multiple rat brain regions in response to chronic nicotine treatment. This suggests that chronic nicotine exposure modulates mitochondrial function, and likely disturbs cellular energy metabolism and the intracellular concentration of oxidative free radicals. The detection of this effect should help us to understand the molecular mechanisms underlying nicotine addiction, and may also suggest molecular targets to consider in human nicotine dependence mechanisms. Future challenges include defining the precise molecular mechanisms that underlie the response of the electron transport system to chronic nicotine treatment and to discover how these mechanisms interact with other cellular events, such as signal transduction, in addicted human smokers and nicotine-treated animals.
