Effects of chronic intermittent ethanol exposure during early and late adolescence on anxiety-like behaviors and behavioral flexibility in adulthood.

Although both humans and laboratory rodents demonstrate cognitive and affective alterations associated with adolescent alcohol exposure, it is still unknown whether the consequences of early initiation of alcohol use differ from those of later binge drinking within the adolescent developmental period. The present study was designed to assess the effects of early and late AIE on (1) anxiety-like behavior under social (modified social interaction test) and non-social test circumstances (modified light/dark box test, elevated plus maze), and (2) behavioral flexibility, indexed via set shifting in males and females. Early-mid adolescent intermittent exposure (early AIE) occurred between postnatal days (P) 25 and 45, whereas late adolescent intermittent exposure (late AIE) was conducted between P45 and P65, with behavioral testing initiated not earlier than 25 days after repeated exposure to ethanol (4.0 g/kg intragastrically, every other day for a total of 11 exposures). Anxiety-like behavior on the EPM was evident in males and females following early AIE, whereas only males demonstrated non-social anxiety on the EPM following late AIE. Social anxiety-like alterations and deficits in behavioral flexibility were evident only in males following early AIE. Taken together, the results of the present study demonstrate a particular vulnerability of young adolescent males to long-lasting detrimental effects of repeated ethanol and an insensitivity of older adolescent females to the intermittent ethanol exposure paradigm.