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Children exposed to alcohol prenatally suffer from a range of physical, neuropathological and behavioral alterations, referred to as Fetal Alcohol Spectrum Disorders (FASD). Both the cerebellum and hippocampus are affected by alcohol exposure during development, which may contribute to behavioral and cognitive deficits observed in children with FASD. Despite the known neuropathology associated with prenatal alcohol exposure, many pregnant women continue to drink (heavy drinkers, in particular), creating a need to identify effective treatments for their children who are adversely affected by alcohol. We previously reported that choline supplementation can mitigate alcohol’s effects on cognitive development, specifically on tasks which depend on the functional integrity of the hippocampus. The present study examined whether choline supplementation could differentially mitigate ethanol’s effects on trace eyeblink classical conditioning (a hippocampal-dependent task) and delay eyeblink classical conditioning (a cerebellar-dependent task). Long-Evans rats were exposed to 5.25 g/kg/day alcohol via gastric intubation from postnatal days (PD) 4-9, a period of brain development equivalent to late gestation in humans. A sham-intubated control group was included. From PD 10-30, subjects received subcutaneous injections of 100 mg/kg choline chloride or vehicle. Beginning on PD 32-34, subjects were trained on either delay or trace eyeblink conditioning. Performance of subjects exposed to alcohol was significantly impaired on both tasks, as indicated by significant reductions in percentage and amplitude of conditioned eyeblink responses, an effect that was attenuated by choline supplementation on the trace, but not delay conditioning task. Indeed, ethanol-exposed subjects treated with choline performed at control levels on the trace eyeblink conditioning task. There were no significant main or interactive effects of sex. These data indicate that choline supplementation can significantly reduce the severity of trace eyeblink conditioning deficits associated with early alcohol exposure, even when administered after the alcohol insult is complete. These findings have important implications for the treatment of fetal alcohol spectrum disorders.

Fetal alcohol spectrum disorders (FASD) are the leading non-genetic cause of neurodevelopmental disability in children. Although alcohol is clearly teratogenic, environmental factors such as gravidity and socioeconomic status significantly modify individual FASD risk despite equivalent alcohol intake. An explanation for this variability could inform FASD prevention. Here we show that the most common nutritional deficiency of pregnancy, iron deficiency without anemia (ID), is a potent and synergistic modifier of FASD risk. Using an established rat model of third trimester-equivalent binge drinking, we show that ID significantly interacts with alcohol to impair postnatal somatic growth, associative learning, and white matter formation, as compared with either insult separately. For the associative learning and myelination deficits, the ID-alcohol interaction was synergistic and the deficits persisted even after the offsprings’ iron status had normalized. Importantly, the observed deficits in the ID-alcohol animals comprise key diagnostic criteria of FASD. Other neurobehaviors were normal, showing the ID-alcohol interaction was selective and did not reflect a generalized malnutrition. Importantly ID worsened FASD outcome even though the mothers lacked overt anemia; thus diagnostics that emphasize hematological markers will not identify pregnancies at-risk. This is the first direct demonstration that, as suggested by clinical studies, maternal iron status has a unique influence upon FASD outcome. While alcohol is unquestionably teratogenic, this ID-alcohol interaction likely represents a significant portion of FASD diagnoses because ID is more common in alcohol-abusing pregnancies than generally appreciated. Iron status may also underlie the associations between FASD and parity or socioeconomic status. We propose that increased attention to normalizing maternal iron status will substantially improve FASD outcome, even if maternal alcohol abuse continues. These findings offer novel insights into how alcohol damages the developing brain.

In contrast to the previously reported neuroprotective potential of antioxidants on EtOH-mediated cerebellar damage, vitamin E supplementation did not diminish EtOH-induced structural and functional damage to the cerebellum in this model of binge EtOH exposure during the brain growth spurt in rats.

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Binge-like ethanol exposure on postnatal days (PD) 4-9 in rodents causes cerebellar cell loss and impaired acquisition of conditioned responses (CRs) during "short-delay" eyeblink classical conditioning (ECC), using optimal (280-350 ms) interstimulus intervals (ISIs). We extended those earlier findings by comparing acquisition of delay ECC under two different ISIs. From PD 4 to 9, rats were intubated with either 5.25 g/kg of ethanol (2/day), sham intubated, or were not intubated. They were then trained either as periadolescents (about PD 35) or as adults (>PD 90) with either the optimal short-delay (280-ms) ISI, a long-delay (880-ms) ISI, or explicitly unpaired CS and US presentations. Neonatal binge ethanol treatment significantly impaired acquisition of conditioning at both ages regardless of ISI, and deficits in the acquisition and expression of CRs were comparable across ISIs. These deficits are consistent with the previously documented ethanol-induced damage to the cerebellar-brainstem circuit essential for Pavlovian ECC.

The extant literature implicates affect repair ability as one source of individual differences in negative affect. Emerging from this literature are three regulatory traits that should predict repair ability (negative mood regulation expectancies, monitoring, labeling), yet no experimental examination of this possibility exists. Two studies explored this issue. Participants (Ns=305, 146) watched negative affect-inducing videos and completed a repair or control writing task, before and after which they reported their affect. Results revealed wide individual differences in repair ability. Specifically, participants with high expectancies of repair success and those who attend to and understand their affect experienced the largest decreases in negative affect and largest increases in positive affect following the repair tasks. These findings advance understanding of individual differences in affect regulation and have implications for future research.