The effects of choline on stress regulation in rats exposed to alcohol during development

Abstract

Includes bibliographical references (p. 55-62).Prenatal alcohol exposure can damage the developing brain, adversely affecting cognitive and emotional development. Animal models indicate that perinatal supplementation with choline (an essential nutrient important for brain development) can reduce the severity of learning deficits associated with developmental alcohol exposure. In addition to altering cognitive systems, choline may also influence stress responses, which could further influence cognitive performance. In fact, prenatal alcohol exposure may cause abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis, a system that regulates stress responses, and recent evidence indicates that choline influences genes important in the regulation of stress. The present study examined if alcohol exposure during the 3rd trimester equivalent affected stress responses, and if any changes were modulated by postnatal choline supplementation. Using a rat model, the study included six treatment groups in a 3 (ethanol-exposed, sham control, non-intubated control) x 2 (choline, vehicle) design. Ethanol (5.25 g/kg/day) was delivered via intragastric intubation from postnatal days (PD) 4 through 9, a period equivalent to the human 3rd trimester. From PD 10-30, subjects were injected subcutaneously with either vehicle (saline) or choline chloride (100 mg/kg/day). On PD 31, subjects were placed on a platform, a mild stressor, in open space for 5 minutes and behaviors were recorded on video and subsequently coded by investigators blind to treatment condition. 100 uL of blood were collected before and after the stressor to determine levels of corticosterone (CORT), a stress hormone. On PD 36, subjects were also tested on an elevated plus maze (EPM), another task used to assess anxiety levels. It was hypothesized that alcohol would increase stress, whereas choline would reduce anxiety-related behaviors, particularly in alcohol-exposed subjects. Alcohol exposure did not significantly alter CORT levels or stress behaviors, suggesting that alcohol exposure during periods of late gestation does not alter stress responses. Moreover, although choline did reduce post-stress CORT levels in alcohol-exposed male subjects, overall, choline did not produce consistent effects on stress responses. These data suggest that choline selectively targets cognitive systems in the brain, and that choline's mitigation of fetal alcohol effects is not mediated by effects on stress