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| Author(s): |
Willian Lazarini Lopes
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | Ribeirão Preto. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) |
| Defense date: | 2017-05-11 |
| Examining board members: |
Claudia Maria Padovan;
Cristina Marta Del Ben
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| Advisor: | Claudia Maria Padovan |
| Abstract | |
Stressors and aversive stimuli are capable of generating changes on physiology and behavior. Serotonin (5-HT) is a neurotransmitter that is involved in the regulation of many, psychological, physiological and behavioral processes, such as adaptation to stressful events. Dysfunctions in the serotonergic system are associated with disorders as depression and anxiety. The restraint stress is able to induce anxiogenic behavioral changes in the elevated plus maze (EPM) test, while the forced swimming test (FST) promotes depressive-like changes in behavior. The major serotoninergic projections to the forebrain are those that starts from the median raphe nucleus (MRN) towards the dorsal hippocampus (DH), and these projections are responsible for adaptation to the stressors. 5-HT7 is a 5-HT receptor present in several brain structures, including MRN. Data from the literature suggest that stress adaptation may involve facilitation of neurotransmission mediated by 5-HT7 in MRN. Thus, the aim of this study was to investigate if 5-HT7 receptors of the MRN are involved in both, anxious and depressive behavior induced by uncontrollable stressors. For this, Wistar rats with an guide-cannunla directed to MRN were underwent to two hours of restraint stress, receiving intra-MRN injections of saline solution, LP- 44 and / or SB-258741 (agonist and antagonista of 5-HT7 receptor, respectively), immediately before or after the restraint stress event. Animals were tested in EPM 24 hours later. In another experimental condition, the animals were submitted to restraint stress and 24 hours later, immediately before the EPM test, they received the intra-MRN treatment. Two control conditions were performed in which the animals were not stressed, receiving intra-NMR injections immediately before or 24 hours before the EPM test. Another animal model used in this study was the forced swimming test (FST) to investigate depressive like-behaviors. Animals receive intra-MRN treatments immediately before or after the pre-test session or immediately before the test (24 hours post-test). Again, two control conditions were performed, without exposure to the pre-test session, with the pharmacological intervention immediately before or 24 hours before the test session of the FST. The behavior of the animals was recorded for 5 minutes in both, EPM and FST, for future analysis. After the behavioral tests, animals were perfused for preservation of tissue and brain removal to further histological analysis of the injection sites. Statistical analysis was performed using one-way ANOVA analysis, according to experience. Animal with injection site outside the MRN were excluded from statistical analysis. The results of this study indicates that activation of 5-HT7 receptors of the MRN increase the exploration of the open arms in the EPM and reduce the immobility in the FST. Injections of SB-258741 prior to LP-44 was able to block the effect produced only by the agonist. These results indicate that activation of the 5-HT7 of the MRN prevents the anxiety and depressive-like behaviors induced by uncontrollabe stress. Thus, this study presents new results showing the direct participation of 5-HT7 receptors that will help the understanding of neurobiological mechanisms behind the adaptation to stress. (AU) | |
| FAPESP's process: | 14/26753-8 - Role of 5-HT7 serotonin receptor subtype of the median raphe nucleus in the behavioral consequences of exposure to restraint stress and forced swimming |
| Grantee: | Willian Lazarini Lopes |
| Support Opportunities: | Scholarships in Brazil - Master |