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Evaluation of the involvement of endovanilloid and endocannabinoid systems in behavioral and plastic consequences after trauma exposure in mice

Grant number: 19/19226-5
Support type:Scholarships in Brazil - Master
Effective date (Start): October 01, 2019
Effective date (End): November 30, 2021
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal researcher:Sabrina Francesca de Souza Lisboa
Grantee:Larissa Fernanda Matias Werworn
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:17/19731-6 - Identification of epigenetic mechanisms induced by stress which modulate endocannabinoid signaling and neuroimmunological mechanisms as new therapeutic targets to treat the posttraumatic stress disorder (PTSD), AP.JP


Post-traumatic stress disorder (PTSD) is a debilitating psychiatric disorder that can develop after exposure to intensely traumatic situations such as physical or sexual violence, war, traffic accident, and others. Nowadays, the treatments approved for PTSD are ineffective, have a considerable latency period, and have numerous adverse effects. Therefore, it is extremely important to study the pathophysiology and neural mechanisms involved in PTSD, in order that more effective medications can be used. One of the systems that may be involved in the pathophysiology of PTSD is endocannabinoid. The objective of the present project is to test the hypothesis that a stress-induced endocannabinoid signaling dysfunction will be involved in PTSD-related behavioral changes as well as in neuroplastic changes. Also, if such changes will be prevented by treatment with drugs that modulate the endocannabinoid system. The specific objectives of the present project will be: to evaluate if the development of anxious behavior and deficits in the extinction of conditioned memories, as well as cellular and molecular alterations resulting from trauma exposure, involve alterations in endocannabinoid signaling and via TRPV1 receptors; and to verify whether facilitation of endocannabinoid signaling via CB1 and CB2 receptors and inhibition of endovanilloid signaling by TRPV1 is able to reverse the long-term consequences of trauma exposure. For this purpose, endocannabinoid-modulating drugs will be administered to wild-type C57 and TRPV1 receptor knockouts mice prior to the realization of the repeated social defeat stress. To assess behavioral alterations, elevated plus maze and contextual conditioned fear tests will be performed. In addition, ATP and endocannabinoid levels in the brain, phenotypic changes in microglia and neuronal activation, dendritic afforestation and gene expression in microglia will be evaluated. (AU)

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