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Investigation of the possible involvement of adenosinergic receptors in the behavioral effects induced by cannabidiol in mice using different animal models

Grant number: 20/04145-7
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2020
Effective date (End): July 31, 2021
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal Investigator:Francisco Silveira Guimaraes
Grantee:João Raphael Campos Alves da Silveira
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

Cannabidiol (CBD), the main non-psychotomimetic constituent of the Cannabis sativa plant, has demonstrated broad therapeutic potential for different neuropsychiatric disorders, including depression and anxiety. However, the mechanisms involved in these effects are not yet fully understood. Results observed in vitro suggest that, among the several mechanisms described, CBD can also inhibit adenosine uptake. Several studies suggest that adenosinergic signaling could be involved in psychiatric disorders such as anxiety and depression. For example, adenosine receptor agonism or antagonism produces anxiolytic or anxiogenic effects, respectively. However, until now, the possible involvement of adenosinergic receptors in CBD's antidepressant and anxiolytic effects has not been investigated. In this sense, the present study aims to evaluate the hypothesis that the adenosinergic system would be involved in the behavioral effects of CBD in different animal models of depression and anxiety. For this, mice will receive an acute systemic injection of caffeine (non-selective antagonist of adenosine receptors: 2.5, 5, 10 and 20 mg / kg), SCH-58261 (selective antagonist of the A2a adenosine receptor: 0.5 and 1 mg / kg), CPT (A1 selective adenosinergic antagonist; 3 and 10 mg / kg), CBD (3, 10 and 30 mg / kg) and vehicle (10 ml / kg). Additional groups will receive combination of ineffective dose of adenosinergic antagonists with effective dose of CBD. The animals will be submitted to the tests of open field, forced swim, elevated plus maze, tail suspension and light-dark transition. (AU)