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Role of Median Raphe Nucleus- Dorsal Hippocampus pathway in the antidepressant effects of treatment with imipramine.

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Author(s):
Kelly da Silva
Total Authors: 1
Document type: Master's Dissertation
Press: Ribeirão Preto.
Institution: Universidade de São Paulo (USP). Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (PCARP/BC)
Defense date:
Examining board members:
Claudia Maria Padovan; Norberto Cysne Coimbra; Sâmia Regiane Lourenço Joca
Advisor: Claudia Maria Padovan
Abstract

Introduction: Depression is a psychiatric disorder whose causes seem to involve chronic exposure to stressors. It is known that the dorsal hippocampus (DH) participates in the adaptation mechanism to aversive stimuli, once the facilitation of serotonergic neurotransmission in this structure reduces the effect of a stressor. The main source of serotonergic innervation to the HD is the median raphe nucleus (MRN). Aim: The aim of this study was to verify if the integrity of the MRN-HD pathway is essential for the antidepressant effects of chronic treatment with imipramine in animals with lesion on serotonergic neurons of MRN submitted to chronic and repeated stress. Materials and Methods: We used male Wistar rats, seven weeks old. The animals were submitted to stereotactic surgery for lesion (or not - control group) on MRN serotonergic neurons. Later, they were divided in groups according to the chronic drug treatment they would receive (Imipramine or Saline). All animals were subjected to chronic (7days/Two hours a day) or acute restraint stress (a single episode of restraint). On the eighth day the animals were tested in the Elevated Plus Maze (EPM). Results: When subjected to acute stress, animals with intact MRN and treated with imipramine showed a higher percentage of time spent in open arms (% TO) and the number of entries in open arms (% FO) when compared to control. Moreover, rats subjected to acute stress and chemically injured showed a greater exploration of open arms (% TO and % FO) when compared with the group without lesion. Imipramine was able to attenuate the effects of stress on animals subjected to chronic stress from both groups, with intact MRN and those with lesion. That was observed on a increase of % TO and % FO when compared with rats treated with saline. The injury on MNR in animals submitted to chronic stress decreased both %TO and % FO. Discussion: Our results showed that the lesion on serotonergic neurons of MNR dont interfere in the behavior of animals in the EPM when subjected to a single stress episode, but decreases the open arm exploration in rats exposed to chronic stress. This effect, however, was attenuated by chronic administration of imipramine. Conclusion: These results suggest that the integrity of the NMnR-HD pathway is not essential for the antidepressant effects Imipramine in the development of tolerance to repeated stress. (AU)

FAPESP's process: 09/11784-7 - Role of median raphe nucleus-dorsal hippocampus pathway in the antidepressant effects of treatment with imipramine in animals submitted to restraint stress
Grantee:Kelly da Silva
Support Opportunities: Scholarships in Brazil - Master