GENE EXPRESSION PROFILE IN THE FRONTAL CORTEX OF RATS SUBJECTED TO CHRONIC UNPREDICTABLE STRESS AND ANTIDEPRESSANT ADMINISTRATION: A COMPARISON WITH HUMAN POSTMORTEM STUDIES.
J.F. Lopez,; S.J. Evans; P.V. Choudary; M.P. Vawter; J. Li; H. Tomita; R.M. Myers; W.E. Bunney; E.G. Jones; S.J. Watson,; H. Akil; R.C. Thompson
Society for Neuroscience 33rd Annual Meeting. 2003.
Studying the effects of stress on gene expression in the brain may help us understand how stressful stimuli are transduced into a depressive episode. Therefore, we used gene array analysis and an animal model of chronic unpredictable stress (CUS) to study gene regulation in rat frontal cortex. We also investigated how administration of the antidepressants fluoxetine, desipramine and bupropion to CUS-treated rats may modify this gene expression. Finally, we investigated whether there was any overlap between the genes regulated by CUS and/or by antidepressants and genes regulated in the prefrontal cortex of subjects with a history of mood disorders. We found that rats subjected to CUS showed significant changes in multiple genes in the frontal cortex. Administration of the three antidepressants prevented many, but not all, of these gene expression changes. Each antidepressant is capable of modulating multiple genes, but there is a subset of these genes that are regulated, in common, by two or more of these antidepressants. Furthermore, a group of genes regulated by CUS and by antidepressants are also regulated in the anterior cingulate and dorsolateral prefrontal cortex of subjects with a history of Major Depression and Bipolar Disorder. The combination of preclinical and human postmortem array analysis studies may allow us to discover new therapeutic targets for antidepressant medications, and give us clues about the pathogenesis of mood disorders. Support Contributed By: The Pritzker Neuropsychiatric Disorder Research Consortium Fund and NIH Conte grant MH60398-03.