Increased ethanol intake is associated with social anxiety in offspring exposed to ethanol on gestational day 12

Prenatal alcohol exposure (PAE) can result in physical, cognitive, and neurological deficits termed Fetal Alcohol Spectrum Disorder (FASD). Deficits in social functioning associated with PAE are frequently observed and persist throughout the lifespan. Social impairments, such as social anxiety, are associated with increased alcohol abuse, which is also highly pervasive following PAE. Yet, the relationship between PAE-induced social alterations and alcohol intake later in life is not well understood. In order to test this relationship, we exposed pregnant female Sprague Dawley rats to a single instance of PAE on gestational day 12, a period of substantial neural development, and tested offspring in adulthood (postnatal day 63) in a modified social interaction test followed by alternating alone and social ethanol intake sessions. Consistent with our previous findings, we found that, in general, PAE reduced social preference (measure of social anxiety-like behavior) in female but not male adults. However, ethanol intake was significantly higher in the PAE group regardless of sex. When dividing subjects according to level of social anxiety-like behavior (low, medium, or high), PAE males (under both drinking contexts) and control females (under the social drinking context) with a high social anxiety phenotype showed the highest level of ethanol intake. Taken together, these data indicate that PAE differentially affects the interactions between social anxiety, ethanol intake, and drinking context in males and females. These findings extend our understanding of the complexity and persistence of PAE's sex-dependent effects into adulthood.