Stress, serotonin, glutamate, and the median raphe nucleus-hippocampus pathway: behavioural and adult hippocampal neurogenesis studies

• Grant number: 07/07134-1
• Support Opportunities: Regular Research Grants
• Duration: March 01, 2008 - November 30, 2010
• Field of knowledge: Humanities - Psychology - Physiological Psychology
• Principal Investigator: Claudia Maria Padovan
• Grantee: Claudia Maria Padovan
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Depression is a very complex disease and may involve exposure to uncontrollable stress.The hippocampus has been implicated in the mechanisms involved in the development of tolerance to chronic stress, since the facilitation of serotonergic neurotransmission attenuates the behavioural effects of previous exposure to stress. The Median Raphe Nucleus (MnRN) gives rise to the main serotoninergic input to the hippocampus. On the other hand, there is an increased density of glutamate NMDA receptors (NMDAr) in the MnRN. When activated by its agonista, NMDAr increases serotonin release within the MnRN and also in the hippocampus. Data show that interference with NMDA neurotransmission in the hippocampus can alter the behavioural consequences of stress. Therefore, considering the role of the MnR-hippocampus pathway in the behavioural consequences of stress, the aim of this work is to verify whether the interference with glutamatergic NMDAr MnRN in different time-points of exposure to forced swim will attenuates the effects of this stressor. Another process that has been described and involves the hippocampus is adult neurogenesis. This process can be modulated by several factors, including stress, glicocorticoids, antidepressive treatments, and environmental enrichment. Adult neurogenesis is controlled by serotonin and glutamate. Although serotoninergic agents such as antidepressants have been shown to increase neurogenesis, the effects of MnRN lesions remain to be elucidated. So, the effects of MnRN lesion on hippocampal neurogenesis in animals chronically stressed and treated or not with Imipramine (a tricyclic antidepressant) will be investigated too. We will also investigate if neurogenesis is related to the cognitive deficits observed in depressive patients, using another two animal models of depression. For this purpose, the learned helplessness and the chronic mild stress models will be used. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ALMEIDA, P. V. G.; TROVO, M. C.; TOKUMOTO, A. M.; PEREIRA, A. C.; PADOVAN, C. M.. Role of serotonin 1A receptors in the median raphe nucleus on the behavioral consequences of forced swim stress. JOURNAL OF PSYCHOPHARMACOLOGY, v. 27, n. 12, p. 7-pg., 2013-12-01. (07/07134-1)

ALMEIDA, P. V. G.; TROVO, M. C.; TOKUMOTO, A. M.; PEREIRA, A. C.; PADOVAN, C. M.. Role of serotonin 1A receptors in the median raphe nucleus on the behavioral consequences of forced swim stress. JOURNAL OF PSYCHOPHARMACOLOGY, v. 27, n. 12, SI, p. 1134-1140, DEC 2013. (07/07134-1)

SILVA, K.; CARVALHO, M. C.; PADOVAN, C. M.. Tolerance to repeated stress in rats with lesions of the serotoninergic neurons of the Median Raphe Nucleus and chronically treated with imipramine. Behavioural Brain Research, v. 302, p. 220-227, APR 1 2016. (09/11784-7, 07/07134-1)