These studies clearly show the importance of mitochondria in the biological response to nicotine. However, the molecular mechanism(s) underlying the involvement of nicotine or abused substances in mitochondrial activities remains largely unknown. On the basis of a cDNA library constructed from purified embryonic ventral mesencephalic dopaminergic neurons, Barrett et al. (2001) developed a microarray consisting of 960 clones that was used to study gene expression changes during methamphetamine neurotoxicity in mouse brain. Expression of genes encoded by the mitochondrial genome, especially that of the cytochrome c oxidase subunit I of complex IV (Mt-co1), proved to be regulated significantly by amphetamine.