Effects of Antidepressant Drug Imipramine on Gene Expression in Rat Prefrontal Cortex

We have investigated gene expression changes produced by acute and chronic daily treatment with a prototypical antidepressant, imipramine, using DNA microarrays. The analysis of similarities in gene expression patterns among functionally related genes revealed four expression profile cluster areas that showed a highly significant overrepresentation of several functional classes. Genes encoding for proteins involved in cAMP metabolism, postsynaptic membrane proteins, and proto-oncogenes were overrepresented in different cluster areas. Furthermore, we found that serine proteases as a group were similarly regulated by chronic antidepressant treatment. Our data suggest that cAMP metabolism, synaptic function, and protein processing by serine proteases may be important targets of antidepressant treatment and potential objects for antidepressant drug development.