Cannabidiol regulation of fear memory processing and associated brain function

• Processo: 12/50896-8
• Linha de fomento: Auxílio à Pesquisa - Regular
• Vigência: 01 de fevereiro de 2013 - 31 de janeiro de 2015
• Área do conhecimento: Ciências Biológicas - Farmacologia - Neuropsicofarmacologia
• Convênio/Acordo: University of Birmingham ; University of Nottingham
• Pesquisador responsável: Francisco Silveira Guimaraes
• Beneficiário: Francisco Silveira Guimaraes
• Pesq. responsável no exterior: Carl William Stevenson
• Instituição no exterior: University of Nottingham, University Park, Inglaterra
• Pesq. responsável no exterior: Jonathan Loon Choon Lee
• Instituição no exterior: University of Birmingham, Inglaterra
• Instituição-sede: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brasil
• Vinculado ao auxílio: 07/03685-3 - Neurotransmissores típicos e atípicos em transtornos neuropsiquiátricos, AP.TEM
• Assunto(s): Transtornos de ansiedade Ansiedade Memória (psicologia) Medo Córtex pré-frontal Canabidiol

Resumo

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)

Publicações científicas

(5)

(Referências obtidas automaticamente do Web of Science e do SciELO, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores)

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. Citações Web of Science: 23.

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. Citações Web of Science: 11.

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. Citações Web of Science: 7.

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. Citações Web of Science: 14.

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. Citações Web of Science: 48.