Adolescent heavy alcohol drinking increases the risk for alcohol use disorders in adulthood, yet mechanisms conferring increased risk are not well understood. We propose that adolescent alcohol drinking shapes alcohol’s aversive or appetitive properties in adulthood. Alcohol normally drives aversive learning and alcohol-predictive cues are avoided. We hypothesize that through adolescent heavy drinking alcohol gains access to appetitive learning. A primary consequence is that alcohol-predictive cues become valued and sought out. To test this hypothesis, we gave genetically heterogeneous, male Long Evans rats voluntary, chronic intermittent access to water or alcohol throughout adolescence and then identified moderate and heavy alcohol drinkers. After a short abstinence period, we assessed the aversive or appetitive properties of alcohol using flavor learning procedures. We compared alcohol to the known appetitive properties of sugar. Flavor learning in adult rats who were alcohol-naïve or adolescent moderate alcohol drinkers revealed alcohol to be aversive and sugar to be appetitive. The same flavor learning procedures revealed both alcohol and sugar to be appetitive in adult rats who were adolescent heavy drinkers. The results demonstrate that alcohol gains access to neurobehavioral circuits for appetitive learning through adolescent heavy alcohol drinking.

Adolescent alcohol drinking increases the risk for alcohol-use disorder in adulthood. Yet, the changes in adult neural function resulting from adolescent alcohol drinking remain poorly understood. We hypothesized that adolescent alcohol drinking alters basolateral amygdala (BLA) function, making alcohol drinking BLA-dependent in adulthood. Male, Long Evans rats were given voluntary, intermittent access to alcohol (20% ethanol) or a bitter, isocaloric control solution, across adolescence. Half of the rats in each group received neurotoxic BLA lesions. In adulthood, all rats were given voluntary, intermittent access to alcohol. BLA lesions reduced adult alcohol drinking in rats receiving adolescent access to alcohol, but not in rats receiving adolescent access to the control solution. The effect of the BLA lesion was most apparent in high alcohol drinking adolescent rats. The BLA is essential for fear learning and is hyper-active in anxiety disorders. The results are consistent with adolescent heavy alcohol drinking inducing BLA hyper-activity, providing a neural mechanism for comorbid alcohol use disorder and anxiety disorders.