1. ¹Division of Molecular Psychiatry, Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
2. ²Department of Psychiatry and Center for Basic Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX, USA
3. ³Clinical Brain Disorders Branch, NIMH, Bethesda, MD, USA

Correspondence: Dr RS Duman, Division of Molecular Psychiatry, Department of Psychiatry, Yale University School of Medicine, 34 Park Street, New Haven, CT 06508, USA. Tel: +1 203 974 7726; Fax: +1 203 974 7724; E-mail: ronald.duman@yale.edu

Received 20 December 2002; Revised 23 June 2003; Accepted 1 July 2003; Published online 8 October 2003.

Abstract

Previous studies demonstrate that chronic, but not acute electroconvulsive seizures (ECS), increases levels of FosB, a long-lasting transcription factor, in the hippocampus, and this effect correlates with the slow onset and long-lasting clinical effects of antidepressant treatment. To understand how FosB mediates long-term plasticity in the hippocampus, we analyzed the gene expression profile of inducible transgenic mice expressing FosB with a highly sensitive microarray assay and a customized computer analysis program. The CCAAT-enhancing binding protein- (C/EBP) was identified as one of the genes downregulated by FosB in the hippocampus. The downregulation of C/EBP in the inducible FosB transgenic mice was confirmed by other quantitative assays including real-time RT-PCR and low density dot blotting. Analysis of the C/EBP expression in the hippocampus of rats treated with ECS revealed that the C/EBP mRNA was also downregulated by chronic, but not acute ECS administration, the most effective treatment for depression. Given the reported role of C/EBP in behavioral conditioning models, it is possible that the FosB-mediated downregulation of C/EBP in the hippocampus may be a molecular mechanism by which antidepressants alleviate some of the symptoms of depressed patients.