EN
Psychotropic drugs activate synchronized patterns of gene expression in the brain. These patterns are connected to biological processes involved in therapeutic as well as adverse drug effects. To reveal the transcriptional networks activated by different classes of psychotropic drugs we compared the effects of antidepressants (e.g. mianserine, fluoxetine), analgesics (e.g. morphine, heroin), psychostimulants (e.g. methamphetamine, cocaine) and antipsychotics (e.g. clozapine, haloperidol) on genomic profile in mouse (C57BL/6J) striatum. We applied a whole-genome microarray (Illumina WG-6) profiling to characterize time-course of transcriptome alterations following acute drug administration (1, 2, 4 and 8h after injection). We identified major drug-regulated expression patterns that are formed by inducible transcriptional networks, as for example: (1) CREB/SRF-dependent genes that appears to be related to dopaminergic activity the striatum, (2) the group of genes controlled at least in part via release of steroid hormones. The data were stored as raw values, fold of change versus saline and P value of drug versus saline comparison in the database (available at www. genes2mind.org). The database interface allows for multidimensional data analysis (PCA), search for drug using genomic signatures and visualize drug-regulated gene transcription patterns. Our results elucidates the networks of drug-induced genes that share common regulatory elements, functional relations and may provide novel diagnostic tools for prediction of drug effectiveness. This work was supported by EU grant LSHM-CT-2004-005166, POIG DeMeTer 3.1 and NN405 274137 grants.