The Effects of Short-Term Stress and Long-Term Fluoxetine Treatment on the Expression of Apoptotic Proteins in the Brain

Abstract

The effects of 2- or 8-week-long daily treatment with fluoxetine at a dose of 7.26–7.70 mg/kg given with drinking water and short-term forced-swim stress on the levels of mRNAs of anti- and pro-apoptotic proteins, that is, Bcl-xL and Bax, respectively, were studied in the brains of adult male rats using the RT-PCR method. Antiapoptotic effects of stress on the expression of these proteins were observed in the hippocampus of rats that were not treated with fluoxetine and in the midbrain after 2 weeks of the antidepressant treatment. Pro-apoptotic effects of stress were revealed in the frontal cortex of animals that were not treated with fluoxetine and after 2 weeks of fluoxetine treatment. An 8-week-long fluoxetine treatment resulted in an increase in the basal Bax expression in the hippocampus and in anti-apoptotic effects in the neocortex, which were more clearly seen after stress. The observed interaction of the effects of stress and fluoxetine on the expression of proteins of neuronal survival and plasticity may provide anti- or proapoptotic action of the antidepressant on the cells of the emotiogenic structures of the brain.