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

• Grant number: 17/26815-1
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): May 01, 2018
• Effective date (End): November 30, 2020
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Sâmia Regiane Lourenço Joca
• Grantee: Gabriela Pandini Silote
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 18/12119-6 - Investigation of the molecular mechanisms involved in the rapid and sustained antidepressant-like effects induced by Cannabidiol, BE.EP.DR

Abstract

Depression is a debilitating psychiatric disorder. Antidepressants have limitations on their use, such as the delay of four to six weeks for onset of therapeutic action and inefficiency in 30-45% of patients.Among the substances that present a better therapeutic profile are cannabidiol (CBD), which showed a rapid and sustained antidepressant effect in animal models. The mechanisms responsible for the effect have not been fully elucidated. However, there is evidence that it involves the activation of 5-HT 1A receptors; rapid increase in BDNF and synaptic proteins in the Prefrontal Cortex (PFC); rapid increase of dendritic afforestation in PFC; and increased hippocampal neurogenesis. Furthermore, a study showed that CBD intra-vmPFC produced an antidepressive-type effect in animals exposed to forced swimming.Thus, it is observed that the mechanism of action occurs in a manner similar to that seen with ketamine. However blocking the CBD of antidepressant effect in the PFC and the details of the downstream of BDNF-TrkB signaling pathway have not been evaluated. The objective of the present study is to evaluate the participation of this pathway in PFC in the antidepressive effect (fast and sustained) of CBD in a preclinical predictive model of antidepressant effect.In addition, investigate the common molecular mechanisms with ketamine that could contribute to the identification of new targets involved in the triggering of antidepressant effects. Therefore, in vitro and in vivo studies comparing the effect of the drug on gene and protein expression, as well as on neuroplasticity (synaptogenesis, dendritic arborization) becomes interesting. (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)

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)