Psychopharmacology (2012) 223:281–297 DOI 10.1007/s00213-012-2714-0 ORIGINAL INVESTIGATION Analysis of region-specific changes in gene expression upon treatment with citalopram and desipramine reveals temporal dynamics in response to antidepressant drugs at the transcriptome level Magdalena Gąska & Maciej Kuśmider & Joanna Solich & Agata Faron-Górecka & Małgorzata J. Krawczyk & Krzysztof Kułakowski & Marta Dziedzicka-Wasylewska Received: 19 December 2011 / Accepted: 30 March 2012 / Published online: 1 May 2012 # The Author(s) 2012. This article is published with open access at Springerlink.com Abstract Rationale The notion that the onset of action of antidepres- sant drugs (ADs) takes weeks is widely accepted; however, the sequence of events necessary for therapeutic effects still remains obscure. Objective We aimed to evaluate a time-course of ADs- induced alterations in the expression of 95 selected genes in 4 regions of the rat brain: the prefrontal and cingulate cortices, the dentate gyrus of the hippocampus, and the amygdala. Methods We employed RT-PCR array to evaluate changes during a time-course (1, 3, 7, 14, and 21 days) of treatments with desipramine (DMI) and citalopram (CIT). In addition to repeated treatment, we also conducted acute treatment (a single dose of drug followed by the same time intervals as the repeated doses). Results Time-dependent and structure-specific changes in gene expression patterns allowed us to identify spatiotemporal differences in the molecular action of two ADs. Singular value Electronic supplementary material The online version of this article (doi:10.1007/s00213-012-2714-0) contains supplementary material, which is available to authorized users. M. Gąska (*) : M. Kuśmider : J. Solich : A. Faron-Górecka : M. Dziedzicka-Wasylewska Department of Pharmacology, Institute of Pharmacology Polish Academy of Sciences, Smętna 12 Street, 31-343 Krakow, Poland e-mail: gaska@if-pan.krakow.pl M. J. Krawczyk : K. Kułakowski Faculty of Physics and Applied Computer Science, AGH University of Science and Technology, al. Mickiewicza 30, 30-059 Kraków, Poland decomposition analysis revealed differences in the global gene expression profiles between treatment types. The numbers of characteristic modes were generally smaller after CIT treat- ment than after DMI treatment. Analysis of the dynamics of gene expression revealed that the most significant changes concerned immediate early genes, whose expression was also visualized by in situ hybridization. Transcription factor bind- ing site analysis revealed an over-representation of serum response factor binding sites in the promoters of genes that changed upon treatment with both ADs. Conclusions The observed gene expression patterns were highly dynamic, with oscillations and peaks at various time points of treatment. Our study also revealed novel potential targets of antidepressant action, i.e., Dbp and Id1 genes. Keywords Antidepressant . Desipramine . Citalopram . Gene expression . RT-PCR . In situ hybridization . Time- course . Delayed onset of action . Rats Introduction Despite the increasing prescription of antidepressant drugs (ADs) and their intensive investigation for almost five deca- des, the mechanisms of their antidepressant action remain unresolved. Some major hypotheses related to depression include monoamine deficiency (Elhwuegi 2004), abnormali- ties in the hypothalamus–pituitary–adrenal (HPA) axis, and the cytokine hypothesis (Leonard and Myint 2009), but the nature and involvement of these components in the etiology of depression remains uncertain. In addition to the monoamine deficiency hypothesis, depression is often associated with the