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Involvement of different sub-populations of serotonergic neurons in the dorsal and median raphe nuclei in female rats exposed to different stressful stimuli


It is well established in the literature that anxiety and depression are more prevalent in women, especially in the cycle phases, stages of life and/or clinical situations (puerperium, perimenopause, bilateral ovariectomy) in which serum concentrations of sexual hormones are low. Considering that serotonergic neurons originated from the Median and Dorsal Raphe Nuclei project toward to the forebrain structures related to the manifestation of these disorders, especially to the Hippocampus and Dorsal Periaqueductal Gray (dPAG), this study aims to investigate the activation of sub-populations of raphe neurons, related to the phases of the hormonal cycle, after submitted to different stressors stimulus. In male rats, the avoidance in the Elevated T Maze increased the activation of serotonergic neurons located in the dorsal, caudal and interfascicular subnuclei of the Dorsal Raphe Nucleus (DRN), as well as in the Median Raphe Nucleus (MRN). The escape enhanced the activation of non-serotonergic neurons in the dorsolateral and dorsomedial subdivisions of the dPAG and in the DRN lateral wings. Therefore, intact or ovariectomized Wistar rats (n=10 animals/group) will be submitted to different behavioral manipulations: Elevated T Maze and acute or chronic stress. After the exposition to the experimental procedures, the brains of the animals will be submitted to immunohistochemistry techniques for neuronal labeling (double labeling for CFOs and tryptophan hydroxylase). The hypothesis that will be tested is that the activation of serotonergic neurons in the dorsal, caudal and interfascicular nuclei of the DRN, and in the MRN, as well as the neuronal activation in the Hippocampus and in the PAG subdivisions occur differently according to the cycle phase, and related to the type of the stressor applied. Behavioral results and data from images, in each experimental phase, will be quantified, organized and submitted to the analysis of variance (ANOVA, One-Way or Two-way according to the variables involved), followed by Duncan's post hoc test. The level of significance adopted will be of 0.05 for all comparisons. Behavioral and immunohistochemistry data will be analyzed together using the Pearson correlation test. (AU)

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