Abstract

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.

Highlights

  • Alcohol is widely used among adolescents and young adults [1]

  • Our results demonstrate that the basolateral amygdala (BLA) plays a minimal role in voluntary alcohol drinking established in adulthood

  • Adolescent heavy alcohol drinking appears to disrupt rapid fear discrimination—resulting in excessive fear to safe cues. In light of these findings, and the observation that adolescent heavy alcohol drinking increases the risk for alcohol use disorder and anxiety disorders, we suggest that adolescent heavy alcohol drinking results in BLA hyper-activity in adulthood, and perhaps for the lifespan

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Summary

Introduction

Alcohol is widely used among adolescents and young adults [1]. Adolescent alcohol drinking, heavy drinking, is associated with increased risk for the development of alcohol use disorder in adulthood [2,3]. Our laboratory recently demonstrated that adolescent heavy alcohol drinking impairs rapid fear discrimination in adulthood [7]. Adolescent heavy drinkers are unable to rapidly reduce fear to safety cues, showing excessive fear. This impairment is likely the result of adolescent alcohol drinking, altering the function of brain regions critical to fear, most notably the basolateral amygdala (BLA) [8,9,10,11,12,13]. We hypothesize that adolescent drinking alters BLA function outside of fear. We hypothesize that alcohol drinking, established in adolescence, depends on the BLA in adulthood

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