Gestational choline supplementation ameliorates T-maze reversal learning deficits induced by first trimester binge alcohol exposure in weanling lambs

• Published in: Alcohol (Fayetteville, N.Y.) Vol. 123; pp. 109 - 120
• Main Authors: Washburn, S., Nation, K., Cudd, T., Stanton, M., Goodlett, C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2025; Elsevier Limited
• Subjects: Alcohol use; Animal cognition; Animal models; Animals; Binge Drinking - complications; Binge Drinking - psychology; Brain damage; Choline; Choline - administration & dosage; Choline - pharmacology; Developmental stages; Dietary Supplements; Disease Models, Animal; Drinking behavior; Estimates; Ethanol; Executive function; FASD; Feeds; Female; Fetal Alcohol Spectrum Disorders - psychology; Fetal alcohol syndrome; Habituation; Intertrial interval; Laboratory animals; Maze learning; Maze Learning - drug effects; Newborn babies; Oral administration; Pregnancy; Pregnancy Trimester, First; prenatal alcohol; Prenatal experience; Prenatal Exposure Delayed Effects - psychology; Psychiatric/Mental Health; Reversal learning; Reversal Learning - drug effects; Sheep; Spatial discrimination learning; T-maze; Weaning; choline; prenatal alcohol; FASD; T-maze
• ISSN: 0741-8329; 1873-6823; 1873-6823
• DOI: 10.1016/j.alcohol.2024.03.007

In rodent models of fetal alcohol spectrum disorders (FASD), cognitive deficits are implicated in impaired T-maze spatial reversal learning. Rat studies have indicated supplemental administration of choline during the developmental period of alcohol exposure can ameliorate spatial reversal deficits. This study tested whether beneficial effects of prenatal choline supplementation could be confirmed in a sheep model of binge exposure in the first trimester equivalent. Two hypotheses were tested: 1) alcohol exposure would produce deficits in reversal of a T-maze position discrimination; and 2) gestational dietary supplementation of choline would ameliorate those deficits. Mated ewes were assigned to one of seven groups—a normal control (NC) group or one of six infusion treatment groups: saline control (SC; isotonic saline), saline control plus choline (SC-CH; isotonic saline plus choline, 10 mg/kg administered orally throughout each day of gestation), binge alcohol (BA; 1.75 g/kg alcohol per infusion day), binge alcohol plus choline (BA-CH; 1.75 g/kg/day alcohol plus choline), heavy binge alcohol (HBA; 2.5 g/kg/day alcohol), or heavy binge alcohol plus choline (HBA-CH; 2.5 g/kg/day alcohol plus choline). The alcohol infusions modeled a weekend binge drinking pattern over the first trimester-equivalent (gestational day 4–41). T-maze training began at 12 weeks of age, with daily sessions occurring 5 days/week. Lambs were given five days of habituation training, followed by five days of position discrimination training (3 trials per daily session, intertrial interval of 3 h, reinforced side randomly assigned across subjects). Lambs were then given 10 days of training on the reversal task. There was no difference among groups during acquisition. Alcohol impaired reversal learning, and choline supplementation mitigated these deficits in the HBA-CH group. These results suggest that maternal dietary choline supplementation can ameliorate or prevent some impairments of executive function in a sheep model of FASD. •Prenatal alcohol impaired reversal learning of a T-maze discrimination in lambs.•Concurrent choline mitigated these deficits in the heavy binge alcohol group.•Choline can ameliorate cognitive impairments linked to executive function in FASD.