Pharmacopsychiatry 2005; 38 - A060
DOI: 10.1055/s-2005-918682

Gene regulation in the dorsal raphe nucleus during chronic social stress and citalopram treatment

G Flügge 1, N Abumaria 1, R Rygula 1, U Havemann-Reinecke 2, E Rüther 2, E Fuchs 1
  • 1Deutsches Primatenzentrum Göttingen
  • 2Klinik für Psychiatrie und Psychotherapie der Universität Göttingen

Changes in the serotonergic system are suspected to play a role in stress-induced neuropathologies and 5-HT neurons in the dorsal raphe nucleus (DRN) are activated by stress. We quantified gene expression in the DRN of male rats subjected to social stress for 5 weeks, and in rats that were stressed and at the same time treated with citalopram (4 weeks).–Subtractive hybridization was performed to clone differentially expressed sequences. Quantitative Real-time PCR showed stress-induced upregulation of two genes related to neurotransmission, one gene involved in neuroplasticity and one related to regulation of transcription. The chronic citalopram treatment normalized expression of these genes. Expression of genes directly related to 5-HT neurotransmission were not affected by chronic social stress. Citalopram downregulated tryptophan hydroxylase 2 in stressed and non-stressed rats, but downregulated the 5-HT1A autoreceptor only in the stressed rats.–In conclusion, chronic stress leads to changes in expression of genes related to neurotransmission/neuroplasticity in the DRN. In contrast, expression of genes directly related to 5-HT neurotransmission appears relatively stable after the 5 weeks of stress. Citalopram does not directly reverse the neuromolecular processes induced by chronic stress in the rat DRN but leads to other changes in gene expression. Supported by DFG Research Center Molecular Physiology of the Brain (CMPB).