Detecting neurodevelopomental effects of early‐gestation ethanol exposure: a non‐human primate model of ethanol drinking during pregnancy

INTRODUCTION: Gestational ethanol exposure is associated with multiple developmental abnormalities, collectively termed fetal alcohol spectrum disorder (FASD). While the majority of women abstain from ethanol following knowledge of pregnancy, one contributing factor to the high FASD prevalence is that pregnancy is not detected until 4–6 weeks. Thus, ethanol consumption continues during the initial stages of fetal development. METHODS: An experimental protocol is described in which rhesus macaques self-administer 1.5 g/kg/day ethanol (or isocaloric maltose-dextrin) prior to pregnancy and through the first 60 days of a 168-day gestation term. Menstrual cycles were monitored, including measurements of circulating estradiol and progesterone levels. The latency to consume 1.5g/kg ethanol and blood ethanol concentration (BEC) were measured. RESULTS: Twenty-eight fetuses (14 ethanol, 14 controls) were generated in this study. Ethanol did not affect menstrual cycles, or the probability of successful breeding. No ethanol-induced gross adverse effects on pregnancy were observed. Individual variability in latency to complete drinking translated into variability in BEC, measured 90 minutes following session start. Drinking latencies in controls and ethanol-drinkers were longer in the second gestational month than in the first. All pregnancies reached the planned experimental time point of G85, G110, or G135, when in utero MRIs were performed, fetuses were delivered by cesarean section, and brains were evaluated with ex vivo procedures, including slice electrophysiology. Fetal tissues have been deposited to the Monkey Alcohol Tissue Research Resource (MATRR). CONCLUSION: This FASD model takes advantage of the similarities between humans and rhesus macaques in gestational length relative to brain development, as well as similarities in ethanol self-administration and metabolism. The daily 1.5 g/kg dose of ethanol through the first trimester does not influence pregnancy success rates. However, pregnancy influences drinking behavior during the second month of pregnancy. Future publications using this model will describe the effect of early-gestational ethanol exposure on anatomical and functional brain development at subsequent gestational ages.