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

Abstract

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.

Effect of Choline Supplementation on Neurological, Cognitive, and Behavioral Outcomes in Offspring Arising from Alcohol Exposure During Development: A Quantitative Systematic Review of Clinical and Preclinical Studies

“…Coles and colleagues () did find that sex was a significant covariate in their generalized linear regression model for analysis of the Bayley Mental Development Index (MDI), but they did not report sex separately in their main data table. However, 5 of the 18 preclinical studies did present data separately for males and females (Balaraman et al., ; Bearer et al., ; Schneider and Thomas, ; Thomas et al., ; Waddell and Mooney, ). Only 1 of these studies (Waddell and Mooney, ) used exposure to alcohol while the placenta was present (gestational day 6 to 20), as opposed to early postnatal exposure during the third‐trimester‐equivalent period.…”

“…However, 5 of the 18 preclinical studies did present data separately for males and females (Balaraman et al., ; Bearer et al., ; Schneider and Thomas, ; Thomas et al., ; Waddell and Mooney, ). Only 1 of these studies (Waddell and Mooney, ) used exposure to alcohol while the placenta was present (gestational day 6 to 20), as opposed to early postnatal exposure during the third‐trimester‐equivalent period. In this study, the greatest amelioration of deficits due to alcohol appeared to occur in male versus female offspring treated with choline.…”

Choline Plus Working Memory Training Improves Prenatal Alcohol-Induced Deficits in Cognitive Flexibility and Functional Connectivity in Adulthood in Rats

“…Poor frontal lobe organization and connectivity is emerging as a paramount feature of FASD [19,20]. In rodents, this loss of adaptive frontal lobe modulation of learned responses can manifest as poor reversal learning and use of inefficient problem-solving strategies [21]. When contingencies change and require "updating", inefficient and perseverative responding is often observed in rats exposed to alcohol (ethanol: EtOH) gestationally [19,21].…”

“…In rodents, this loss of adaptive frontal lobe modulation of learned responses can manifest as poor reversal learning and use of inefficient problem-solving strategies [21]. When contingencies change and require "updating", inefficient and perseverative responding is often observed in rats exposed to alcohol (ethanol: EtOH) gestationally [19,21]. Adolescence is a time during which working memory capacity and efficiency reach adult levels [18].…”

“…As the frontal cortices mature, the ability to hold items in mind and adapt to changing contingencies becomes more efficient [22][23][24]. We previously reported improved performance on the attentional set shifting and reversal learning task (ASST-R) in rats exposed prenatally to EtOH when both postnatal choline supplementation and working memory training were combined in the juvenile phase [21]. Males exhibited more general impairments in ASST-R than females, but both sexes did exhibit more errors and higher trials to criterion in some phases of the task [21].…”