Adolescent cannabinoid exposure modulates the vulnerability to cocaine-induced conditioned place preference and DNMT3a expression in the prefrontal cortex in Swiss mice

Autor(es)

Gobira, P. H. ^[1] ; Roncalho, A. L. ^[1] ; Silva, N. R. ^[2] ; Silote, G. P. ^[1] ; Sales, A. J. ^[2] ; Joca, S. R. ^{[3, 1]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto FCFRP, Dept Biomol Sci, Cafe Av S-N, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Sch Med Ribeirao Preto FMRP, Dept Pharmacol, Ribeirao Preto, SP - Brazil

^[3] Aarhus Univ, Dept Biomed, Aarhus - Denmark

• Tipo de documento: Artigo Científico
• Fonte: Psychopharmacology; v. 238, n. 11 JUL 2021.
• Citações Web of Science: 1

Resumo

Rationale Cannabis sativa is the most widely used drug by adolescents globally. The recreational use of synthetic cannabinoids by teenagers has also grown in recent years. Despite the wrong perception that exposure to these drugs does not cause harm, repeated exposure to cannabinoids at early stages of life compromises important maturation processes and brain development. Chronic early cannabinoid use has been related to a higher risk of psychiatric outcomes, including cocaine addiction. Evidence suggests that exposure to natural and synthetic cannabinoids during adolescence modifies molecular and behavioral effects of cocaine in adulthood. Responses to cocaine are regulated by epigenetic mechanisms, such as DNA methylation, in the brain's reward regions. However, the involvement of these processes in modulation of the vulnerability to the effects of cocaine induced by prior exposure to cannabinoids remains poorly understood. Objectives Investigate whether exposure to the synthetic cannabinoid WIN55,212-2 during adolescence modulates anxiety- and depression-like behavior, memory, and cocaine reward in adult mice. We also evaluated whether exposure to cannabinoids during adolescence modulates the expression of enzymes that are involved in DNA methylation. Results Exposure to WIN55,212-2 during adolescence did not alter anxiety- or depressive-like behavior. However, prior exposure to cannabinoids inhibited cocaine-induced conditioned place preference without modulating cocaine-induced hyperlocomotion, accompanied by an increase in expression of the enzyme DNA methyltransferase 3a (DNMT3a) in the prefrontal cortex. Conclusions Our findings suggest that exposure to WIN55,212-2 during adolescence leads to changes in DNMT3a expression, and this pathway appears to be relevant to modulating the rewarding effects of cocaine. (AU)

• Processo FAPESP: 17/19284-0 - Envolvimento da acetilação de histonas na modulação da vulnerabilidade aos efeitos da cocaína induzida pela exposição a canabinoides durante a adolescência
• Beneficiário: Pedro Henrique Gobira Nunes
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 17/24304-0 - Novas perspectivas no emprego de fármacos que modificam neurotransmissores atípicos no tratamento de transtornos neuropsiquiátricos
• Beneficiário: Francisco Silveira Guimaraes
• Modalidade de apoio: Auxílio à Pesquisa - Temático