Investigation of the molecular mechanisms involved in the rapid and sustained antidepressant-like effects induced by Cannabidiol

• Grant number: 18/12119-6
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: September 29, 2018
• End date: September 28, 2019
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Sâmia Regiane Lourenço Joca
• Grantee: Gabriela Pandini Silote
• Supervisor: Gregers Wegener
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Aarhus University, Denmark
• Associated to the scholarship: 17/26815-1 - Investigation of the involvement of the BDNF-TrkB pathway in the mechanism of action of the rapid and sustained antidepressant-like effect induced by canabidiol, BP.DR

Abstract

Depression is a debilitating and disabling psychiatric disorder. Dysfunction on pre-frontal cortex (PFC) have been related to depression. Ketamine is an important drug that produces rapid and sustained antidepressant effects, which seems to involve activation of the BDNF-TrkB-mTOR pathway, with subsequent activation of MEK and PI3K, leading to increased synaptogenesis. We have recently shown that cannabidiol (CBD), a non-psychostimulant cannabinoid, also showed rapid and sustained antidepressant effect in preclinical models. The mechanisms responsible for these effects seem to involve rapid increase of BDNF and synaptic proteins levels, as well as increased dendritic arborization in the PFC. However, it is not known which are the triggering mechanisms of such neuroplastic effects. Since some of the behavioral effects of CBD have been linked to 5-HT1A and/or CB1 receptor activation, the aim of this study is to investigate if the rapid neuroplastic effects induced by CBD would be mediated by 5-HT1A and/or CB1 receptor signaling with subsequent activation of the BDNF-TrkB-mTOR pathway and increased synaptogenesis in the PCF. Furthermore, we will investigate if CBD would share common mechanisms of action with ketamine in triggering these behavioral and neuroplastic effects.

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)

SILOTE, G. P.; ESKELUND, A.; JOCA, S. R. L.; WEGENER, G.. Gender-specific antidepressant effect of cannabidiol in flinders sensitive line rats. European Neuropsychopharmacology, v. 29, p. 1-pg., 2019-12-01. (17/26815-1, 12/17626-7, 18/12119-6)

SILOTE, GABRIELA P.; DE OLIVEIRA, SABRINA F. S.; RIBEIRO, DEIDIANE E.; MACHADO, MAYARA S.; ANDREATINI, ROBERTO; JOCA, SAMIA R. L.; BEIJAMINI, VANESSA. Ketamine effects on anxiety and fear-related behaviors: Current literature evidence and new findings. PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, v. 100, JUN 8 2020. (17/26815-1, 18/12119-6)

SILOTE, GABRIELA P.; GATTO, MICHELLE C.; ESKELUND, AMANDA; GUIMARAES, FRANCISCO S.; WEGENER, GREGERS; JOCA, SAMIA R. L.. Strain-, Sex-, and Time-Dependent Antidepressant-like Effects of Cannabidiol. PHARMACEUTICALS, v. 14, n. 12, p. 19-pg., 2021-12-01. (17/26815-1, 18/12119-6)