Gene expression in the brain from antidepressants treated mouse using DNA microarray

Abstract

The molecular and biological bases for the mechanisms of antidepressants are based on the monoamine depletion hypothesis. However, we do not yet know the full cascade of mechanisms responsible for the therapeutic effect of antidepressants. To identify the genes involved in the therapeutic mechanisms of various antidepressants, we used a cDNA microarray system containing 30000 clones with isolated total RNA from each treated rat brain. In the present study, we demonstrated gene expression changes of treatment with a tricyclic antidepressant (imipramine), a selective serotonin reuptake inhibitor (fluoxetine), monoamine oxidase inhibitor (phenelzine) and psychoactive herbal extracts of PM011. The expression of 35, 20, 37 and 44 genes were decreased and 21, 49, 35 and 27 were over‐expressed by imipramine, fluoxetine, phenelzine and PM011, respectively.Members of signal transduction, factors related to protein metabolism, cell survival, ligand‐receptor interaction, were some of the genes with altered expression. These data demonstrate that antidepressants interfere with the expression of a large array of genes involved in signaling, survival and protein metabolism.The results support the hypothesis that the therapeutic effect of these antidepressants is much more complex and not confined to a reuptake inhibition of neurotransmitters and inhibition of MAOThis work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government(MEST) (No. 2009‐0063466).