Identification of genes regulated by chronic social stress in the rat dorsal raphe nucleus.

1. Changes in the serotonergic (5-HT) system are suspected to play a role in stress-induced neuropathologies and neurochemical measures indicate that serotonergic neurons in the dorsal raphe nucleus (DRN) are activated during stress. In the present study we analyzed gene expression in the DRN after chronic social stress using subtractive cDNA hybridization. 2. In the resident intruder paradigm, male Wistar rats were chronically stressed by daily social defeat during 5 weeks, RNA was isolated from their DRN, cDNA was generated, and subtractive hybridization was performed to clone sequences that are differentially expressed in the stressed animals. 3. From the cDNA libraries that were obtained, we selected the following genes for quantitative Real-time PCR: Two genes related to neurotransmission (synaptosomal associated protein 25 and synaptic vesicle glycoprotein 2b), a glial gene presumptively supporting neuroplasticity (N-myc downstream-regulated gene 2), and a gene possibly related to stress-induced regulation of transcription (CREB binding protein). These four genes were upregulated after the chronic social stress. Quantitative Western blotting revealed increased expression of synaptosomal associated protein 25 and synaptic vesicle glycoprotein 2b. 4. Genes directly related to 5-HT neurotransmission were not contained in the cDNA libraries and quantitative Real-time PCR for the serotonin transporter, tryptophan hydroxylase 2 and the 5-HT(1A) autoreceptor confirmed that these genes are not differentially expressed after 5-weeks of daily social stress. 5. These data show that 5 weeks of daily social defeat lead to significant changes in expression of genes related to neurotransmission and neuroplasticity in the DRN, whereas expression of genes directly related to 5-HT neurotransmission is apparently normal after this period of chronic stress.