Brain DNA damage and behavioral changes after repeated intermittent acute ethanol withdrawal by young rats

Priscila A. Costa, Jefferson H Z Poli, Nathalia D M Sperotto, Dinara J. Moura, Jenifer Saffi, Maurício S. Nin, Helena M T Barros*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


Rationale: Alcohol addiction causes severe problems, and its deprivation may potentiate symptoms such as anxiety. Furthermore, ethanol is a neurotoxic agent that induces degeneration and the consequences underlying alcohol-mediated brain damage remain unclear. Objectives: This study assessed the behavioral changes during acute ethanol withdrawal periods and determined the levels of DNA damage and reactive oxygen species (ROS) in multiple brain areas. Methods: Male Wistar rats were subjected to an oral ethanol self-administration procedure with a forced diet where they were offered 8 % (v/v) ethanol solution for 21 days followed by five repeated 24-h cycles alternating between ethanol withdrawal and re-exposure. Control animals received an isocaloric control diet without ethanol. Behavioral changes were analyzed on ethanol withdrawal days in the open-field (OF) and elevated plus-maze (EPM) tests within the first 6 h of ethanol deprivation. The pre-frontal cortex, hypothalamus, striatum, hippocampus, and cerebellum were dissected for alkaline and neutral comet assays and for dichlorofluorescein ROS testing. Results: The repeated intermittent ethanol access enhanced solution intake and alcohol-seeking behavior. Decreased exploratory activity was observed in the OF test, and the animals stretched less in the EPM test. DNA single-strand breaks and ROS production were significantly higher in all structures evaluated in the ethanol-treated rats compared with controls. Conclusions: The animal model of repeated intermittent ethanol access induced behavioral changes in rats, and this ethanol exposure model induced an increase in DNA single-strand breaks and ROS production in all brain areas. Our results suggest that these brain damages may influence future behaviors.

Original languageEnglish
Article number4015
Pages (from-to)3623-3636
Number of pages14
Issue number19
Publication statusPublished - 1 Oct 2015
Externally publishedYes


  • Alcohol withdrawal
  • Anxiety-like
  • Brain DNA damage
  • Ethanol
  • ROS


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