Repeated exposure to cocaine promotes structural and electrophysiological changes in the mesolimbic encephalic pathway, which regulates behaviors related to abuse. These complex adaptations in the brain are mediated by dynamic patterns of gene expression that are translated into enduring changes critically regulated by epigenetics mechanisms, including histone acetylation. Indeed, recent works have demonstrated the important role of this epigenetic regulatory event in mediating lasting effects of cocaine in animal models of drug addiction. However, little is known about interference of environmental factors and other drugs of abuse in this mechanism, and their relevance in vulnerability to cocaine responses later in life.Environmental influences on adolescence seem to be determinant for adult behavior, possibly through epigenetic changes. Exposure to Cannabis sativa, the most popular illegal drug used among adolescents, during this period of development, may have permanent consequences on several brain functions in later adult life. Studies in humans and animals suggest that exposure to THC as well as its synthetic analogues during adolescence intensifies the behavioral effects of cocaine in adults. However, the involvement of epigenetic mechanisms in this process remains to be elucidated. Thus, this study was designed to test the involvement of histone acetylation in the increased vulnerability to cocaine-effects induced by previous exposure tocannabinoids.
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