Prenatal choline supplementation mitigates behavioral alterations associated with prenatal alcohol exposure in rats

Abstract

Background: Prenatal alcohol exposure can alter physical and behavioral development, leading to a range of fetal alcohol spectrum disorders. Despite warning labels, pregnant women continue to drink alcohol, creating a need to identify effective interventions to reduce the severity of alcohol's teratogenic effects. Choline is an essential nutrient that influences brain and behavioral development. Recent studies indicate that choline supplementation can reduce the teratogenic effects of developmental alcohol exposure. The present study examined whether choline supplementation during prenatal ethanol treatment could mitigate the adverse effects of ethanol on behavioral development.

Methods: Pregnant Sprague-Dawley rats were intubated with 6 g/kg/day ethanol in a binge-like manner from gestational days 5-20; pair-fed and ad libitum chow controls were included. During treatment, subjects from each group were intubated with either 250 mg/kg/day choline chloride or vehicle. Spontaneous alternation, parallel bar motor coordination, Morris water maze, and spatial working memory were assessed in male and female offspring.

Results: Subjects prenatally exposed to alcohol exhibited delayed development of spontaneous alternation behavior and deficits on the working memory version of the Morris water maze during adulthood, effects that were mitigated with prenatal choline supplementation. Neither alcohol nor choline influenced performance on the motor coordination task.

Conclusions: These data indicate that choline supplementation during prenatal alcohol exposure may reduce the severity of fetal alcohol effects, particularly on alterations in tasks that require behavioral flexibility. These findings have important implications for children of women who drink alcohol during pregnancy.

Figure 1

Percent of subjects that spontaneously alternated on PD 28–30. Ethanol-exposed subjects alternated significantly less than controls, an effect that was significantly mitigated with prenatal choline supplementation. EtOH = ethanol-exposed; PF = pair fed controls; LC = lab chow controls ** = significantly different from all other groups except the PF + Choline group

Figure 2

(A) Mean (+ SEM) path length to find the platform in the Morris Water Maze task over testing days. Prenatal alcohol exposure did not significantly affect acquisition, although PF subjects were significantly impaired compared to both EtOH and LC subjects. Choline supplementation improved spatial learning performance among LC controls, producing a significant effect of choline. (B) Mean (+ SEM) heading angle (chosen path compared to direct path to platform) during Morris water maze acquisition. Choline supplementation significantly improved performance accuracy in LC, but not EtOH or PF subjects, producing a significant of choline. No significant effect of ethanol was found. ***= significantly different from all other groups

Figure 3

Mean (+ SEM) path length during the test trials (A) of the spatial working memory task. During the test trials, ethanol-exposed subjects that were not choline supplemented took longer path lengths to find the platform, compared to all other group, except the PF + Choline group. Thus, choline supplementation mitigated ethanol-related deficits. Panel B shows the savings from training to test trial, which serves as a measure of memory retention of the platform’s position. Ethanol-exposed subjects that did not receive choline supplementation showed no evidence of savings, whereas all other groups did. Indeed, the ethanol-exposed subjects treated with choline performed at levels similar to those of the control subjects. ** = significantly different from all other groups except the PF + Choline group