Cannabidiol regulation of fear memory processing and associated brain function

• Grant number: 12/50896-8
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2013
• End date: January 31, 2015
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Agreement: University of Birmingham ; University of Nottingham
• Principal Investigator: Francisco Silveira Guimaraes
• Grantee: Francisco Silveira Guimaraes
• Principal researcher abroad: Carl William Stevenson
• Institution abroad: University of Nottingham, University Park, England
• Principal researcher abroad: Jonathan Loon Choon Lee
• Institution abroad: University of Birmingham, England
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 07/03685-3 - Typical and atypical neurotransmitters in neuropsychiatric disorders, AP.TEM

Abstract

Anxiety disorders such as phobias and post-traumatic stress are common and often debilitating diseases linked to abnormally persistent memories of fearful events. Although psychological and drug therapies are available, these treatments show limited effectiveness and can cause adverse side effects, highlighting the urgent need for better therapies to treat these disorders. Cannabidiol, the main non-psychotropic phytocannabinoid present in the Cannabis sativa plant, is a drug that has shown great promise for treating anxiety disorders. We have shown that cannabidiol reduces fear in various animal models of anxiety and have recently extended these findings to show that it also reduces fear memory expression. Interestingly, cannabidiol has also been shown to enhance fear memory extinction, the process by which psychological therapy can reduce fear memory persistence. However, the pharmacological mechanisms and brain sites involved in mediating these effects remain unclear or unknown. In this multi-disciplinary project we will combine behavioral, pharmacological, electrophysiological and molecular biology techniques to determine the neurochemical and neural circuit mechanisms underlying the effects of cannabidiol on fear memory processing. Specifically, we will examine the roles of endocannabinoid transmission and prefrontal cortex-hippocampus circuit function in mediating the effects of cannabidiol on the expression and extinction of contextual fear memory in rats. Understanding the basic mechanisms underlying cannabidiol's effects on behaviour and brain function has important translational implications for its potential use in treating anxiety. (AU)

Scientific publications

(6)

(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)

LEE, JONATHAN L. C.; BERTOGLIO, LEANDRO J.; GUIMARAES, FRANCISCO S.; STEVENSON, CARL W.. Cannabidiol regulation of emotion and emotional memory processing: relevance for treating anxiety-related and substance abuse disorders. British Journal of Pharmacology, v. 174, n. 19, SI, p. 3242-3256, OCT 2017. (12/50896-8)

JURKUS, REGIMANTAS; DAY, HARRIET L. L.; GUIMARAES, FRANCISCO S.; LEE, JONATHAN L. C.; BERTOGLIO, LEANDRO J.; STEVENSON, CARL W.. Cannabidiol Regulation of Learned Fear: Implications for Treating Anxiety-Related Disorders. FRONTIERS IN PHARMACOLOGY, v. 7, NOV 24 2016. (12/50896-8)

FOGACA, MANOELA V.; SONEGO, ANDREZA B.; RIOLI, VANESSA; GOZZO, FABIO C.; DALE, CAMILA S.; FERRO, EMER S.; GUIMARAES, FRANCISCO S.. Anxiogenic-like effects induced by hemopressin in rats. Pharmacology Biochemistry and Behavior, v. 129, p. 7-13, FEB 2015. (12/17626-7, 12/50896-8)

FOGACA, M. V.; REIS, F. M. C. V.; CAMPOS, A. C.; GUIMARAES, F. S.. Effects of intra-prelimbic prefrontal cortex injection of cannabidiol on anxiety-like behavior: Involvement of 5HT(1A) receptors and previous stressful experience. European Neuropsychopharmacology, v. 24, n. 3, p. 410-419, MAR 2014. (12/17626-7, 12/50896-8)

LEE, JONATHAN L. C.; BERTOGLIO, LEANDRO J.; GUIMARAES, FRANCISCO S.; STEVENSON, CARL W.. Cannabidiol regulation of emotion and emotional memory processing: relevance for treating anxiety-related and substance abuse disorders. British Journal of Pharmacology, v. 174, n. 19, p. 15-pg., 2017-10-01. (12/50896-8)

BATISTA, PRISCILA A.; FOGACA, MANOELA V.; GUIMARAES, FRANCISCO S.. The endocannabinoid, endovanilloid and nitrergic systems could interact in the rat dorsolateral periaqueductal gray matter to control anxiety-like behaviors. Behavioural Brain Research, v. 293, p. 182-188, OCT 15 2015. (12/17626-7, 12/50896-8)