Prenatal alcohol exposure and adolescent stress increase sensitivity to stress and gonadal hormone influences on cognition in adult female rats

Physiol Behav. 2015 Sep 1;148:157-65. doi: 10.1016/j.physbeh.2015.02.033. Epub 2015 Feb 21.


Abnormal activity of stress hormone (hypothalamic-pituitary-adrenal [HPA]), and gonadal hormone (hypothalamic-pituitary-gonadal [HPG]) systems is reported following prenatal alcohol exposure (PAE). PAE increases vulnerability of brain regions involved in regulation of these systems to stressors or challenges during sensitive periods of development, such as adolescence. In addition, HPA and HPG functions are linked to higher order functions such as executive function (EF), with dysregulation of either system adversely affecting EF processes, including attention and response inhibition, that influence cognition. However, how HPA and HPG systems interact to influence cognitive performance in individuals with an FASD is not fully understood. To investigate, we used a rat model of moderate PAE. Adolescent female PAE and control offspring were exposed to 10days of chronic mild stress (CMS) and cognitive function was assessed on the radial arm maze (RAM) in adulthood. On the final test day, animals were sacrificed, with blood collected for hormone analyses, and vaginal smears taken to assess estrus stage at the time of termination. Analyses showed that adolescent CMS significantly increased levels of CORT and RAM errors during proestrus in adult PAE but not control females. Moreover, CORT levels were correlated with estradiol levels and with RAM errors, but only in PAE females, with outcome dependent on adolescent CMS condition. These results suggest that PAE increases sensitivity to the influences of stress and gonadal hormones on cognition, and thus, in turn, that HPA and HPG dysregulation may underlie some of the deficits in executive function described previously in PAE females.

Keywords: Adolescent stress; Cognition; FASD; Female rat; Gonadal hormones; HPA axis; Prenatal alcohol exposure.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Factors
  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Central Nervous System Depressants / toxicity*
  • Cognition Disorders / blood
  • Cognition Disorders / etiology*
  • Corticosterone / blood*
  • Estradiol / blood*
  • Estrous Cycle / blood
  • Ethanol / toxicity*
  • Female
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Pregnancy
  • Prenatal Exposure Delayed Effects / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Sex Factors
  • Stress, Psychological / physiopathology*
  • Time Factors


  • Central Nervous System Depressants
  • Ethanol
  • Estradiol
  • Corticosterone