title: Brain DNA damage and behavioral changes after repeated intermittent acute ethanol withdrawal by young rats.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Laboratory of Neuropsycopharmacology, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Priscila A
authors.initials: PA
authors.lastname: Costa
authors.forename: Jefferson H Z
authors.initials: JH
authors.lastname: Poli
authors.forename: Nathalia D M
authors.initials: ND
authors.lastname: Sperotto
authors.forename: Dinara J
authors.initials: DJ
authors.lastname: Moura
authors.forename: Jenifer
authors.initials: J
authors.lastname: Saffi
authors.forename: Maurício S
authors.initials: MS
authors.lastname: Nin
authors.forename: Helena M T
authors.initials: HM
authors.lastname: Barros
mesh_terms: D000367:Age Factors; D000437:Alcoholism / Q000150:complications / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000209:etiology / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects* / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000209:etiology / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D000431:Ethanol