Adolescent intermittent ethanol impairs behavioral flexibility in a rat foraging task in adulthood

Alcohol exposure is linked to behavioral flexibility deficits in humans, but it is unclear when the critical exposure occurred or if alcohol exposure alone is sufficient to produce behavior deficits. Increasing evidence shows that binge levels of alcohol during adolescence are particularly harmful to the brain, producing physiological and behavioral effects that can persist into adulthood. The present study determined whether adolescent intermittent ethanol (AIE) in rats impaired action selection in a discriminative stimulus task using a foraging response. Rats were exposed to ethanol during adolescence (5 g/kg/day, IG, 2-days-on/2-days-off, postnatal day 25-54). In adulthood, they learned to dig for food reward buried in one of two media, cued with one of two odors. AIE and control rats both learned to discriminate between olfactory cues, but AIE rats were impaired when reversing that learned association (first intra-dimensional reversal). However, AIE rats were faster to reinstate the original odor discrimination rule (second reversal), suggesting perseverative behavior. Next, the reward location was cued by digging media rather than odor. Both groups learned this extra-dimensional shift; however, control rats were slower to reach criterion. These findings are consistent with studies of people with substance abuse disorder, who learn new stimulus-response associations similarly to, or better than, control subjects, but perseverate when attempting to replace a well-learned association. These data suggest that adolescent binge-alcohol exposure contributes to behavioral flexibility deficits observed in adulthood.