Prenatal Ethanol Exposure Impairs Executive Function in Mice into Adulthood

Abstract

Despite evidence that prenatal alcohol exposure (PAE) can lead to a wide range of impairments in cognitive, social, and emotional behaviors, drinking during pregnancy remains common. Although there is a general understanding that high levels of drinking during pregnancy are unsafe, conflicting evidence regarding the impact of low intake may account for the persistence of this behavior. To investigate the effects of PAE on learning and executive control, we utilized a voluntary paradigm where pregnant mice had access to a saccharin-sweetened 10% alcohol solution for 4hours, during the dark cycle, throughout gestation. Male and female offspring were tested as adults on a touch-screen discrimination and reversal task mediated by corticostriatal circuits. Consistent with previous findings, PAE did not lead to gross morphological, motor, or sensory alterations in offspring. Both PAE and saccharin control female mice were slower to acquire the discrimination than males, but PAE did not impair associative learning in either sex. During reversal, PAE led to a specific and significant impairment in the early phase, where cortical control is most required to flexibly alter choice behavior. PAE mice showed a significant increase in maladaptive perseverative responses but showed intact learning of the new association during late reversal. Previously, data from clinical studies have suggested that executive control deficits may underlie cognitive, as well as social, problems seen in adolescents with documented PAE. These data demonstrate that even more moderate alcohol exposure during development can lead to impaired cognitive functioning well into adulthood.