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Role of 5-HT7 and 5-HT1A receptors localized at the dorsal hippocampus and the Median Raphe Nucleus of rats on the behavioural consequences of stress


Major Depression is a complex disease which etiology has been associated to a central serotoninergic disfuncion and/or exposure to inescapable/uncontrollable stress. On the other hand, adaptation to stressful situations involves changes in the functioning of serotoninergic systems mediated by different receptors. Serotoninergic projection from the Median Raphe Nucleus (MnRN) to the Dorsal Hippocampus (DH) have been related to the disconnection of previous aversive memories associated to behavioural changes. Facilitation of 5-HT1a receptors (5-HT1aR) mediated neurotransmission in the DH or MnRN attenuates the behavioural consequences of exposure to different innescapable stressors. This effect is partially blocked by previous treatment with 5-HT1aR selective antagonists, suggesting the involvement of other subtypes of serotonin receptors, such as the 5-HT7 (5-HT7R) receptor subtype. Antidepressant effects have been described after treatmet with 5-HT7R antagonists. However, there are few studies showing the effects of such drugs when treatment is given into the DH or MnRN of rats exposed to different animal models of depression. Moreover, the importance of the integrity of the MnRN-DH pathway in rats with lesions of the serotoninergic neurons of the MnRN on the antidepressant effects of drugs such as Fluoxetine (SSRI) and Desipramine (SNRI) are not known.Therefore, the aim of this project is to investigate the role of 5-HT7R localized at the DH and the MnRN of rats exposed to different animal models of depression: forced restraint associate to the Elevated Plus Maze Test, Forced Swim Test and Learned Helplessness. The development of tolerance to repeated stress in rats with lesions of the MnRN-DH pathway will also be investigated. (AU)

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