Adolescent Intermittent Ethanol Exposure Alters Exploratory and Affective Behaviors, and CerebellarGrin2BExpression in Adulthood

AbstractMore than 90% of alcohol consumption by young people is in the pattern binge drinking. During adolescence, the brain undergoes maturational changes that influence alterations in behavior control, affective behaviors, and cerebellar brain volume and function in adulthood. We investigated long-term impacts of adolescent binge alcohol exposure on affective behaviors and cerebellar gene expression in male and female mice. We exposed C57BL/6J mice to adolescent intermittent ethanol (AIE) or air (control) vapor inhalation from postnatal day 28-42. After prolonged abstinence, in young adulthood we assessed behavior in the open field, light/dark, tail suspension, and forced swim stress tests to determine changes in affective behaviors including anxiety-like, depressive-like, and stress reactivity behavior. mRNA levels ofFMR1and other interacting gene expressions (Grin2a, Grin2B, Grm5, PSD-95, and Eaat1) were measured in the cerebellum of control and adult AIE-exposed mice. In adult AIE-exposed mice, we show decreased movement in the open field in both sexes and modest changes in females in anxiety-like behavior (center zone activity). In the forced swim stress test, adult AIE-exposed male mice spent less time immobile compared to their same-sex controls, indicative of sex-specific changes in stress reactivity. Male and female AIE-exposed mice showed increasedGrin2BmRNA expression in the adult cerebellum compared to their same-sex controls. Together, these data show that adolescent binge-like ethanol exposure altered affective behaviors and modifiedGrin2Bexpression in adulthood. This indicates the cerebellum may serve as an important brain region that is susceptible to long-term molecular changes with adolescent alcohol exposure.HighlightsAdolescent intermittent ethanol (AIE) exposure decreased exploratory behavior in adulthood in male and female mice.In females, but not males, AIE increased anxiety-like behavior.In males, but not females, AIE reduced stress reactivity in adulthood.These findings indicate sex differences in the enduring effects of AIECerebellarGrin2B mRNAlevels were increased in adulthood in both male and female AIE-exposed mice.These findings add to the small, but growing literature on behavioral AIE effects in mice, and establish cerebellar excitatory synaptic gene expression as an enduring effect of adolescent ethanol exposure.