Abstracts

Rationale: Fetal exposure to anti-epileptic drugs presents a risk to the unborn offspring. In humans, children with fetal valproic acid exposure often present with developmental delay and later cognitive impairment and intellectual disability. Rodent models of valproic acid exposure vary in dosing schedule, teratology and effects, but few have examined the developmental trajectories and the long-term emotional, attentional and cognitive consequences.Methods: Pregnant mice (C57BL/6) were given a single mid-gestation dose of valproic acid to mimic first trimester exposure in humans. Control dams were given phosphate buffered saline vehicle alone. Offspring were monitored for weight and developmental milestones until adulthood. Adult offspring were tested on a battery of emotional and cognitive behaviors.Results: Mice that received valproic acid in utero were similar to vehicle control treated mice in overall open field exploration. Tests of anxiety, including elevated plus maze and light-dark choice assays, showed no difference between treatment groups or sex. However, the male valproic acid treated mice demonstrated altered stereotypical responses. Social interactions and frontal cortical mediated cognition were assessed.Conclusions: Mice that received in utero valproic acid demonstrated similar behavioral phenotypes to children of epileptic mothers. Current experiments are investigating methods to define molecular mechanisms of valproic acid developmental disruptions.