Abstract

Gene Expression Profile in the Brain of Rats Subjected to Chronic Unpredictable Stress and Antidepressant Administration: A Comparison With Human Postmortem Studies

J.F. López; S.J. Evans; M.P. Vawter; P.V. Choudary; J. Li; H. Tomita; R.M. Myers; W.E. Bunney; E.G. Jones; S.J. Watson; H. Akil; R.C. Thompsone
Albert J. Silverman Research Conference. 2005.

Abstract

Background: Using animal models to study the effects of stress and antidepressant administration on gene expression may help us understand how stressful stimuli are transduced into a depressive episode, and give us insights into the therapeutic mechanisms of antidepressants. Methods: Our laboratory has used microarray (gene chip) analysis and a rat model of chronic unpredictable stress (CUS) to study gene regulation in brain. We have also investigated how administration of the antidepressants fluoxetine, desipramine, and bupropion, to CUS-treated rats may modify gene expression. Finally, we have investigated whether there is any overlap between genes regulated by CUS and/or by antidepressants, and genes regulated in the prefrontal cortex of subjects with a history of mood disorders. Results: Rats subjected to CUS exhibit significant changes in multiple genes in the frontal cortex. Administration of the three antidepressants prevents 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 Unipolar Depression and Bipolar Disorder. These genes include transcription factors, growth factors, and molecules involved in synaptic plasticity. Conclusions: 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.