Jd. Thomas et al., Neonatal choline supplementation ameliorates the effects of prenatal alcohol exposure on a discrimination learning task in rats, NEUROTOX T, 22(5), 2000, pp. 703-711
Prenatal alcohol exposure can disrupt brain development and lead to a myria
d of behavioral alterations, including motor coordination deficits, hyperac
tivity, and learning deficits. There remains a need, however, to identify t
reatments and interventions for reducing the severity of alcohol-related ne
urodevelopmental disorders. Some of the alcohol-induced deficits in learnin
g may be related to alterations in cholinergic functioning. Interestingly,
there is a growing literature demonstrating that pre- and/or early postnata
l choline supplementation can lead to long-term enhancement in learning and
memory and cholinergic activity in rats. The present study examined whethe
r such early choline supplementation might counter the effects of prenatal
alcohol treatment on a visuospatial discrimination task. Pregnant Sprague-D
awley rats were randomly assigned to one of three prenatal treatment groups
. One group received a liquid diet containing 35% ethanol-derived calories
(EDC) from gestational day (GD) 6-20. A second group served as a pair-fed (
PF) control group and the third group served as an ad lib lab chow (LC) con
trol. On postnatal day (PD) 2, pups were assigned within-litter to one of t
hree postnatal treatments: choline, saline vehicle, or no treatment. Cholin
e and vehicle pups were intubated with a choline chloride solution or vehic
le daily from PD 2 to 21, whereas the non-treated pups were handled daily b
ut not intubated. On PD 45, subjects were tested on a visuospatial discrimi
nation task. Ethanol-exposed subjects who were not treated neonatally with
choline committed a significantly greater number of errors both during acqu
isition and during delayed discrimination training compared to both PF and
LC controls. Neonatal choline treatment significantly improved performance
on the discrimination task in all groups; however, the beneficial effects o
f choline were significantly larger in ethanol-exposed subjects. Indeed, th
e performance of ethanol-exposed pups treated with neonatal choline did not
differ from any of the PF or LC groups on any measure. Thus, early postnat
al choline supplementation significantly attenuated the effects of prenatal
alcohol on this learning task. Importantly, these effects were not due to
the acute effects of choline, but rather to longterm changes in brain and b
ehavioral development. These data suggest that early dietary interventions
may reduce the severity of fetal alcohol effects. (C) 2000 Elsevier Science
Inc. All rights reserved.