A first study compared the time-dependent effects of acute exposure to six drugs of abuse (nicotine, ethanol, morphine, heroin, cocaine and methamphetamine) on gene expression (analyzed 1, 2, 4 and 8 h after injection) in the striatum of C57Bl/6J mice [48]. Clustering analysis identified two main modules of drug-responsive genes. A first module was selectively induced by psychostimulants (cocaine and methamphetamine) at early time-points and opioids (morphine and heroin) at later time-points, and contained several genes associated with transcription regulation, protein phosphatase activity and circadian rhythms. Induction of these genes by cocaine could be blocked by pre-treatment with dopamine D1 receptor antagonist or by a MEK1/2 inhibitor. The second module was subdivided into three subsets of genes selectively induced 1 to 2 h, 2 to 4 h or 4 h after injection of ethanol, respectively. These subsets were enriched in transcripts involved in 1. Small GTPase-mediated signal transduction, apoptosis and cell cycle control; 2. Enzyme inhibitor activity, apoptosis and stress response; and 3. Magnesium ion binding and morphogenesis. Interestingly, morphine and heroin produced a similar time-dependent gene expression pattern within
