A swine model for Fetal Alcohol Spectrum Disorder - The effect of maternal free-choice ethanol consumption on the behavior of female offspring
Backus, Brittany L.
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Pigs are a great biomedical model and are very similar to humans in anatomy, physiology, and behavior. Antidotal stories have always portrayed pigs as a species that will freely drink and get intoxicated, and the pig has similar ethanol pharmacokinetics as humans. Therefore, we used the domestic pig as a novel model for Fetal Alcohol Spectrum Disorder. Pig ethanol pharmacokinetics are similar to the human, but this has only been shown in younger pigs. In order to show the ethanol absorption, distribution and elimination of ethanol in a model that represents oral consumption of ethanol, we intragastrically gavaged pregnant sows with 3 g/kg of 30% ethanol. We found this dose produced high blood ethanol concentrations (BEC) and that pigs were intoxicated. But variability between pigs was high and a long plateau phase was observed in ethanol metabolism. More pigs, better blood collection location, and longer collection period are needed to determine ethanol pharmacokinetics in older, pregnant pigs. Fetal Alcohol Spectrum Disorder (FASD) is an umbrella term that represents the broad range of developmental, behavioral, mental and anatomical deficits caused by the teratogenic effects of ethanol consumption during pregnancy. Many factors influence the severity of FASD and how much ethanol reaches the fetus, such as peak blood ethanol concentrations, dose of ethanol, rate of consumption, and timing and pattern of exposure. Our objective was to use a free-choice drinking paradigm in a pig model to evaluate the behavioral implications of offspring prenatally exposed to ethanol. Coping style was assessed by a backtest at 5 d of age. Anxiety was measured in an isolation test (14 d of age), while locomotion, anxiety, and novelty seeking was measured in an open field test (28 d of age). Social status was measured within the litter by teat order (7 d of age), against an unfamiliar pig in the socialization test (16 d of age), and within the home pen by a food competition test (150 d of age). Learning and cognition were assessed in a series of maze tests at 35 d of age. Texas Tech University, Brittany L. Backus, December 2013 viii The effects of prenatal alcohol exposure (PAE) were assessed using a Completely Randomized Design in experiment 1. All pigs remained with the birth sow throughout the lactation period and only two treatments were assessed, control (CON) and ethanol exposed (ETOH). In experiment 2, we used a Randomized Complete Block Design, in which pigs were cross fostered to the opposite rearing treatment or remained with the birth sow; control-control (CC), control-ethanol (CE), ethanol-control (EC) and ethanol-ethanol (EE). Freely drinking sows consumed an average of 2 g/kg of 20% ethanol the first 10 wk of gestation which did not affect the litter sizes and numbers of pigs born dead or alive, or offspring weights at birth, weaning and harvest, but differences in behavior tests were observed. Prenatal exposure to ethanol made ETOH pigs in experiment 1 low responders to stress as assessed by the backtest, but EE pigs in experiment 2 were higher responders to stress. Isolation was more fearful for CON pigs and a novel environment and object elicited a larger fear response for CON and EC pigs. Ethanol pigs were more active in the open field test. Ethanol pigs were quicker at completing the mazes and more pigs successfully completed them compared to CON pigs regardless if more errors were made. Prenatal exposure increased aggression and therefore social status at an early age, but at adolescence this was reversed and ETOH pigs were more submissive. The submissive social status and PAE at adolescence increased ethanol consumption in EE pigs when individually housed. Behavioral findings in the pig model are similar to FASD characteristics in humans. Differences between treatments in both experiment 1 and 2 indicate prenatal ethanol treatments as well as lactation rearing environment influenced the behavior of pigs, and that the pig could be a good model for FASD. However, this is the first research of its kind, and more needs to be completed to develop a replicable pig model.