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

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  • P. H. Gobira, Universidade de São Paulo
  • ,
  • A. L. Roncalho, Universidade de São Paulo
  • ,
  • N. R. Silva, Universidade de São Paulo
  • ,
  • G. P. Silote, Universidade de São Paulo
  • ,
  • A. J. Sales, Universidade de São Paulo
  • ,
  • S. R. Joca

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.

Sider (fra-til)3107-3118
Antal sider12
StatusUdgivet - nov. 2021

Bibliografisk note

Funding Information:
Pedro Henrique Gobira received a postdoctoral fellowship from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; no. 2017/19284–0). SJ received a productivity fellowship from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; no. 304780/20189). This work was funded by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES; Finance Code 001), FAPESP (no. 2017/24304–0), and Innovation Fund Denmark (grant no. 8020-00310B).

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

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