IDENTIFICATION OF GENES REGULATED BY MULTIPLE ANTIDEPRESSANTS IN RAT HIPPOCAMPUS
Society for Neuroscience 33rd Annual Meeting. 2003.
Antidepressant medications are the mainstay treatment for Major Depressive Disorder. Although most antidepressant medications currently in use are known to alter monoaminergic function, the precise mechanism by which antidepressants exert their therapeutic action is still unknown. It is also not known whether different classes of antidepressants act through, an as yet unidentified, common "distal" biochemical pathway. We have used microarray analysis to identify genes regulated by antidepressants belonging to three different classes (fluoxetine, bupropion, desipramine) in male rat hippocampus. After screening more than 8,000 genes with the Affymetrix U34A GeneChip, we identified several genes whose expression is altered by chronic (four weeks) antidepressant administration. Although each antidepressant is capable of modulating multiple genes, a subset of these genes are regulated, in common, by two or more of these antidepressants. 169 genes were found to be regulated by both bupropion and desipramine, 57 genes were regulated by both fluoxetine and bupropion, 77 genes were regulated by both desipramine and fluoxetine, and 28 genes where regulated by the three antidepressants. Real Time RT-PCR confirmed the regulation of a subset of these genes. These antidepressant-regulated genes fall into many biochemical categories, including transcription factors, growth factors, and cell surface proteins. The identification of genes regulated by multiple antidepressants in rat hippocampus lends support to the hypothesis that antidepressants may act via a common distal biochemical pathway. We will present our array data and our strategy for confirming and refining lists of genes potentially involved in antidepressant action. Support Contributed By: This work was supported by the Pritzker Neuropsychiatric Disorders Research Consortium Fund and NIMH Conte Grant MH60398-03. We acknowledge participation of all consortium members in this work.