Repeated cycles of binge-like ethanol exposure induce immediate and delayed neurobehavioral changes and hippocampal dysfunction in adolescent female rats

Behav Brain Res. 2018 Sep 17:350:99-108. doi: 10.1016/j.bbr.2018.05.007. Epub 2018 May 9.

Abstract

Binge-like ethanol intake (BEI) is a socioeconomical problem among adolescents and increasingly affects women. BEI can leave a long-term imprint in the brain, but it is unknown if its effect on cognition and anxiety is cumulative on repeated binge-ethanol episodes. We now submitted female Wistar rats to repeated cycles of binge-like ethanol treatment by intragastrically administering ethanol (3.0 g/kg/day, 20% w/v ethanol; 3 days on/4 days off) starting at postnatal day 35 (PND35). To investigate the short-term effects of BEI during adolescence, rats underwent 1 or 4 cycles of BEI, being evaluated at PND37 and PND58, respectively: both groups displayed anxiety-like behavior in the open field and elevated plus-maze tests, as well as short-term memory deficits in the object recognition task; this was associated with transient decreases of BDNF levels and increases of GFAP levels in the hippocampus. To evaluate the short- and long-lasting effects of BEI in adulthood, rats were subjected to 8 cycles of BEI and evaluated after 7.5 h (PND86) or after 14 days of ethanol withdrawal (PND100). This caused a persistent anxiogenic profile whereas recognition memory was impaired on the short-term, but not 14 days post-administration. The reduced BDNF level observed shortly after BEI recovered upon withdrawal, whereas increased GFAP immunoreactivity was persistent up to 14 days post-administration in adulthood. These findings show that repeated binge-like ethanol episodes from adolescence to adulthood in female rats cause consistent and long-term alterations of anxiety and hippocampal astrogliosis, whereas they trigger a recognition memory deficit paralleled by lower hippocampal BDNF levels, both recovering upon ethanol withdrawal.

Keywords: Adolescence; Anxiety; Astrogliosis; BDNF; Binge drinking; Cognition.

MeSH terms

  • Animals
  • Anxiety / etiology*
  • Anxiety / physiopathology
  • Binge Drinking / physiopathology*
  • Binge Drinking / psychology*
  • Female
  • Glial Fibrillary Acidic Protein / metabolism
  • Hippocampus / drug effects*
  • Hippocampus / growth & development
  • Hippocampus / physiopathology
  • Memory Disorders / etiology*
  • Memory Disorders / physiopathology
  • Rats, Wistar
  • Sexual Maturation
  • Time Factors

Substances

  • GFAP protein, rat
  • Glial Fibrillary Acidic Protein