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Involvement of histone acetylation in modulating vulnerability to the cocaine-effects induced by exposure to cannabinoids during adolescence

Grant number: 17/19284-0
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): January 29, 2018
Effective date (End): January 28, 2019
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal researcher:Sâmia Regiane Lourenço Joca
Grantee:Pedro Henrique Gobira Nunes
Supervisor abroad: David Dietz
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Research place: State University of New York, Buffalo State (SUNY), United States  
Associated to the scholarship:16/00715-8 - Sensitization to cocaine induced by previous exposure to cannabinoids: Involvement of epigenetic mechanisms induced by DNA methylation, BP.PD


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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Scientific publications (4)
(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)
MITRA, SWARUP; GOBIRA, PEDRO H.; WERNER, CRAIG T.; MARTIN, JENNIFER A.; IIDA, MADOKA; THOMAS, SHRUTHI A.; ERIAS, KYRA; MIRACLE, SOPHIA; LAFARGUE, CHARLES; AN, CHUNNA; et al. A role for the endocannabinoid enzymes monoacylglycerol and diacylglycerol lipases in cue-induced cocaine craving following prolonged abstinence. ADDICTION BIOLOGY, v. 26, n. 5, . (17/19284-0)
WERNER, CRAIG T.; MITRA, SWARUP; AUERBACH, BENJAMIN D.; WANG, ZI-JUN; MARTIN, JENNIFER A.; STEWART, ANDREW F.; GOBIRA, PEDRO H.; IIDA, MADOKA; AN, CHUNNA; COBB, MORIAH M.; et al. Neuroadaptations in the dorsal hippocampus underlie cocaine seeking during prolonged abstinence. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v. 117, n. 42, p. 26460-26469, . (17/19284-0)
WERNER, C. T.; MITRA, S.; MARTIN, J. A.; STEWART, A. F.; LEPACK, A. E.; RAMAKRISHNAN, A.; GOBIRA, P. H.; WANG, Z. -J.; NEVE, R. L.; GANCARZ, A. M.; et al. Ubiquitin-proteasomal regulation of chromatin remodeler INO80 in the nucleus accumbens mediates persistent cocaine craving. SCIENCE ADVANCES, v. 5, n. 10, . (17/19284-0)
GOBIRA, P. H.; RONCALHO, A. L.; SILVA, N. R.; SILOTE, G. P.; SALES, A. J.; JOCA, S. R.. Adolescent cannabinoid exposure modulates the vulnerability to cocaine-induced conditioned place preference and DNMT3a expression in the prefrontal cortex in Swiss mice. Psychopharmacology, v. 238, n. 11, . (17/19284-0, 17/24304-0)

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