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Sensitization to cocaine induced by previous exposure to cannabinoids: Involvement of epigenetic mechanisms induced by DNA methylation

Grant number: 16/00715-8
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): June 01, 2016
Effective date (End): July 31, 2020
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal Investigator:Sâmia Regiane Lourenço Joca
Grantee:Pedro Henrique Gobira Nunes
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated scholarship(s):17/19284-0 - Involvement of histone acetylation in modulating vulnerability to the cocaine-effects induced by exposure to cannabinoids during adolescence, BE.EP.PD

Abstract

Several evidence suggests that repeated exposure to cocaine promotes structural and electrophysiological modifications in encephalic mesolimbic pathway, that result in behavioral changes related to abuse. These neural adaptations may be due to modulation of gene expression, which are critically regulated by epigenetic mechanisms. Recently, the influence of these regulatory mechanisms in mediating the effects induced by cocaine has been investigated. Treatment with this psychostimulant may, for example, modify the levels and the activity of enzymes involved in DNA methylation processes. This mechanism also seems to be important to the withdrawal and relapse phenomena. However, little is known about the interference of environmental factors and other drugs of abuse in this epigenetic mechanism and its relevance to vulnerability to cocaine responses. In this sense, early environmental influences in life seems to be determinants for adult behavior, possibly through epigenetic alterations. Studies in humans and laboratory animals suggest that previous exposure to THC as well as their synthetic analogues, intensifies the effects of cocaine in adults. However the role of epigenetic mechanisms in these processes remains poorly elucidated. Thus, this study was designed to test the hypothesis that DNA methylation processes contribute to the increase in vulnerability to cocaine, induced by prior exposure to cannabinoids.