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Abstract: Stressful life events are able to induce long-term modifications in physiological and neuroendocrine parameters that are related to the onset of several psychiatric disorders. To gain information on molecular modifications involved in long-term changes triggered by stress, we evaluated gene expression in the hippocampus of rats exposed to a single social defeat session. In the social defeat model, the experimental animal is defeated by a dominant male. The defeat induced an increase in body temperature, in distress vocalisations, in serum corticosterone levels and in anxiety-related behaviour measured with an open field test applied 6 h after the exposure to the dominant rat. In the open field test, anxiety-related behaviours were not detectable anymore 30 h after the exposure to the dominant rat and mRNA levels were evaluated at this time-point. The mRNA levels of genes modulated by stress (corticotropin-releasing factor; corticotropin-releasing factor receptor 1; corticotropin-releasing factor binding protein; mineralocorticoid and glucocorticoid receptors; Ca2+/calmodulin-dependent protein kinase-like kinase; Krox20; Bcl-2) and control genes (glyceraldehyde-3-phosphate dehydrogenase; β-actin and cyclophilin A) were measured with real-time reverse transcription polymerase chain reaction. Corticotropin-releasing factor and glucocorticoid receptor mRNA levels were significantly modulated by the stress procedure, both genes showing an increase in rats exposed to a social defeat. No expression level differences were detected for the other genes. In conclusion, we report that 30 h after an acute social stress, a modification in mRNA levels can be detected in rat hippocampus, thus suggesting potential candidate genes involved in mediating long-term responses. [Copyright &y& Elsevier]

The neurotrophin brain-derived neurotrophic factor (BDNF) is considered to be a key factor for neuronal survival, differentiation and plasticity. According to a proposed hypothetical model BDNF expression might play a central role in the pathogenesis of depression. The BDNF gene is rather complex in its structure and it can express four different mRNA isoforms by alternative splicing, each producing the same protein. This might reflect fine tuning of gene regulation by different signalling networks. Since the BDNF gene has been reported to be upregulated by antidepressants, the expression of the four BDNF mRNA isoforms was measured by real-time quantitative RT-PCR in rat hippocampi after chronic and acute treatment with the antidepressant drug fluoxetine and GR205171, a selective NK-1 receptor antagonist with anxiolytic-like properties. The aim of this study was to test the hypothesis of differential regulation of the mRNA isoforms by those compounds. Our results indicate that the expression of BDNF mRNA isoforms is not affected by chronic or acute treatment with fluoxetine or GR205171. [Copyright &y& Elsevier]