Adolescent ethanol sensitivity may predict temporal patterns of anxiety-like behavior following ethanol withdrawal in male rats

<i>Background:</i> Adolescent binge drinking increases the risk of alcohol use disorder, and individual differences in initial ethanol sensitivity may predict susceptibility to anxiety-like behaviors following ethanol withdrawal in adolescent males. It is still unclear whether these anxiety-like alterations are driven by specific subpopulations.<i>Objectives:</i> This study examined the impact of initial responsiveness to the socially facilitating/inhibiting effects of ethanol in adolescent males on anxiety-like behavior during ethanol withdrawal.<i>Methods:</i> Male rats (<i>n</i> = 72) were divided into socially facilitated, non-responding, and socially inhibited phenotypes using a tertile split based on changes in social behavior after an acute ethanol challenge. Ethanol or water exposure occurred from P28-53. Social anxiety-like behavior was assessed during acute withdrawal from single and repeated binge episodes and during protracted abstinence. Nonsocial anxiety-like changes were also evaluated during protracted abstinence.<i>Results:</i> Males initially facilitated by ethanol displayed transient social anxiety-like behavior during acute withdrawal from chronic exposure (<i>F</i>_2,41 = 4.418, <i>p</i> < .05), but not during protracted abstinence. Males inhibited by ethanol showed anxiety-like behavior during acute withdrawal from chronic exposure (<i>F</i>_2,42 = 4.345, <i>p</i> < .05), but unlike facilitated males, these effects persisted into protracted abstinence (<i>p</i> < .01). Only non-responsive males displayed social anxiety-like behavior during all withdrawal timepoints (<i>F</i>_1,22 = 30.87, <i>p</i> < .0001). Additionally, ethanol-exposed males displayed increased nonsocial anxiety-like behavior regardless of phenotype (<i>F</i>_1,66 = 12.04, <i>p</i> < .001).<i>Conclusions:</i> These results suggest that, in this rodent model, adolescent individual differences in initial ethanol sensitivity may predict ethanol withdrawal vulnerability. These findings inform research aimed at identifying adolescent boys in clinical settings who are vulnerable to developing alcohol use disorder.