Evaluation of the Cannabidiol effects under neuroimmunoendocrine and behavioral alterations induced by stress in mice

• Grant number: 16/14282-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: October 01, 2016
• End date: October 31, 2020
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Francisco Silveira Guimaraes
• Grantee: Alice Hartmann dos Santos
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 12/17626-7 - Cellular and molecular mechanisms involved in the role of atypical neurotransmitters in neuropsychiatric disorders, AP.TEM
• Associated scholarship(s): 18/17387-9 - Evaluation of the endocannabinoid signaling and cannabidiol effects on immunological parameters in a psychopathological mouse model of trait anxiety, BE.EP.DR

Abstract

The neurobiology of depressive disorders is not fully understood, but it is proposed that interactions among the immune system, stress, and central nervous system (CNS) result in neuroimmunoendocrine alterations which facilitate the emergence of depression. It is known that there is an increase of pro-inflammatory cytokines in depressive people or in animals subjected to stressors. Among these mediators is interleukin-1b (IL-1b), widely described as neuroinflammatory agent, antineurogenic and depressive-like behavior inductor in experimental animals. The NFkB route and NLRP3 inflammasome (a cytosolic multiprotein complex activated in response to tissue damage, cellular metabolism alterations and infections) mediate IL-1b transcription and function, leading to the activation of innate immune system and inflammation. The NLRP3 inflammasome activation has been widely described in animal models of stress and depressive patients have an increase in its expression in blood mononuclear cells. The hyperactivation of the hypothalamic-hypophysis-adrenal axis in depression is observed in both humans and in experimental animals and it has been reported that glucocorticoids sensitize the NLRP3 pathway. Cannabidiol (CBD), a non-psychotomimetic compound of Cannabis sativa, has many therapeutic effects already described - among which stand out the antidepressant-like and anxiolytic-like in animal models as well as an anti-inflammatory activity. However, the interaction between CBD and the immune system in the CNS, as well as their possible involvement on the behavioral effects of this compound, are still unknown. Thus, this project aims to assess whether CBD is able to prevent depressive-like and anxiety-like behaviors and neuroimmunoendocrine alterations induced by stress model in mice. It is also intended to check the involvement of the NLRP3 inflammasome on the CBD 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)

HARTMANN, ALICE; FASSINI, ALINE; SCOPINHO, AMERICA; CORREA, FERNANDO M. A.; GUIMARAES, FRANCISCO S.; LISBOA, SABRINA F.; RESSTEL, LEONARDO B. M.. Role of the endocannabinoid system in the dorsal hippocampus in the cardiovascular changes and delayed anxiety-like effect induced by acute restraint stress in rats. JOURNAL OF PSYCHOPHARMACOLOGY, v. 33, n. 5, p. 606-614, MAY 2019. (17/19731-6, 16/14282-6, 13/13721-8, 14/24828-0, 12/17626-7, 13/00249-9)

HARTMANN, ALICE; LISBOA, SABRINA FRANCESCA; SONEGO, ANDREZA BUZOLIN; COUTINHO, DEBORA; GOMES, FELIPE VILLELA; GUIMARAES, FRANCISCO SILVEIRA. Cannabidiol attenuates aggressive behavior induced by social isolation in mice: Involvement of 5-HT1A and CB1 receptors. PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, v. 94, AUG 30 2019. (16/14282-6, 10/17343-0, 17/24304-0, 11/22523-0, 17/19731-6)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SANTOS, Alice Hartmann dos. Evaluation of the Cannabidiol effects under neuroimmunoendocrine and behavioral alterations induced by stress in mice. 2020. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.