Recently, our laboratory published a study demonstrating that aspirin (150 mg/kg s.c.) injected one hour prior to administration of 5.8 g/kg alcohol on Day 10 of pregnancy in C57BL/6J antagonized the teratogenic actions of alcohol (Randall and Anton, 1984). More specifically, aspirin pretreatment reduced the incidence of birth defects by fifty percent and prevented the increase in prenatal mortality produced by alcohol. The present proposal represents an attempt to follow-up these data with regard to generalizability and to evaluate possible explanations of the observation. A series of studies is proposed to evaluate the effect of aspirin pretreatment on alcohol-induced teratogenesis at various times during pregnancy, in different strains of mice, and following """"""""chronic"""""""" rather than """"""""acute"""""""" alcohol exposure. Studies evaluating possible mechanisms will investigate the effects of aspirin pretreatment on alcohol-induced corticosterone levels, alcohol-induced hypothermia, and alcohol-induced stimulation of prostaglandins (PGE) in morse embryos. The protective effect of aspirin on alcohol-induced teratogenesis warrants additional study since it is one of the first reports of pharmacologic intervention. Additionally, it may lead to the identification of the pathophysiological mechanism of some fetal alcohol effects.
