Choline and Working Memory Training Improve Cognitive Deficits Caused by Prenatal Exposure to Ethanol

Nutrients. 2017 Sep 29;9(10):1080. doi: 10.3390/nu9101080.


Prenatal ethanol exposure is associated with deficits in executive function such as working memory, reversal learning and attentional set shifting in humans and animals. These behaviors are dependent on normal structure and function in cholinergic brain regions. Supplementation with choline can improve many behaviors in rodent models of fetal alcohol spectrum disorders and also improves working memory function in normal rats. We tested the hypothesis that supplementation with choline in the postnatal period will improve working memory during adolescence in normal and ethanol-exposed animals, and that working memory engagement during adolescence will transfer to other cognitive domains and have lasting effects on executive function in adulthood. Male and female offspring of rats fed an ethanol-containing liquid diet (ET; 3% v/v) or control dams given a non-ethanol liquid diet (CT) were injected with choline (Cho; 100 mg/kg) or saline (Sal) once per day from postnatal day (P) 16-P30. Animals were trained/tested on a working memory test in adolescence and then underwent attentional set shifting and reversal learning in young adulthood. In adolescence, ET rats required more training to reach criterion than CT-Sal. Choline improved working memory performance for both CT and ET animals. In young adulthood, ET animals also performed poorly on the set shifting and reversal tasks. Deficits were more robust in ET male rats than female ET rats, but Cho improved performance in both sexes. ET male rats given a combination of Cho and working memory training in adolescence required significantly fewer trials to achieve criterion than any other ET group, suggesting that early interventions can cause a persistent improvement.

Keywords: T-maze; cognitive flexibility; delayed non-matching to place; fetal alcohol spectrum disorder; nutrition.

MeSH terms

  • Animals
  • Attention / drug effects
  • Behavior, Animal / drug effects
  • Choline / administration & dosage
  • Choline / therapeutic use*
  • Cognition / drug effects
  • Cognition Disorders / prevention & control*
  • Combined Modality Therapy
  • Dietary Supplements
  • Disease Models, Animal*
  • Female
  • Fetal Alcohol Spectrum Disorders / drug therapy
  • Fetal Alcohol Spectrum Disorders / therapy*
  • Injections, Subcutaneous
  • Learning / drug effects*
  • Learning Disabilities / prevention & control*
  • Male
  • Maze Learning / drug effects
  • Memory and Learning Tests
  • Memory, Short-Term / drug effects
  • Nootropic Agents / administration & dosage
  • Nootropic Agents / therapeutic use*
  • Rats, Long-Evans
  • Reversal Learning / drug effects
  • Sex Characteristics


  • Nootropic Agents
  • Choline