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Involvement of the medial prefrontal cortex (mPFC) in the rapid and sustained effect of drugs in a model of depression resistant to conventional antidepressants: possible involvement of endocannabinoid modulation on the cortical glutamatergic system

Grant number: 22/00197-8
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): February 01, 2022
Effective date (End): January 31, 2024
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal researcher:Francisco Silveira Guimaraes
Grantee:Lívea Dornela Godoy
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:17/24304-0 - New perspectives in the use of drugs that modify atypical neurotransmitters in the treatment of neuropsychiatric disorders, AP.TEM

Abstract

The need to develop new therapeutic targets for the treatment of neuropsychiatric disorders is a consensus in the scientific literature. Endocannabinoids (eCBs) have been proposed as a possible target, and studies by our group have shown the therapeutic potential of drugs that act on these atypical neurotransmitters in anxiety disorders, depression, psychosis, Parkinson's and neurodegeneration. Cannabidiol (CBD), a non-psychotomimetic phytocannabinoid that, among other effects, can increase concentrations of the endocannabinoid anandamide, is already in clinical trials for use in several of these conditions. However, many important questions still remain open such as the mechanisms involved and possible interaction between eCBs and glutamatergic system in the prefrontal cortex. Therefore, this project will continue investigation, seeking to understand which intracellular pathways would be involved in the rapid and sustained antidepressant effect induced by CBD. We also hope to identify the specific participation of endocannabinoids in the disinhibition of interneurons, and which subsequent mechanisms would be related to the rapid and sustained effects.

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