LAUSR

Studies in rats have revealed marked age differences in sensitivity to the aversive properties of ethanol, with a developmental insensitivity to ethanol aversion that is most pronounced during pre- and early adolescence, declining thereafter to reach the enhanced aversive sensitivity of adults. The adolescent brain undergoes significant transitions throughout adolescence, including in regions linked with drug reward and aversion; however, it is unknown how ontogenetic changes within this reward/aversion circuitry contribute to developmental differences in aversive sensitivity. The current study examined early adolescent (postnatal day [P]28-30) and adult (P72-74) Sprague-Dawley male rats for conditioned taste aversion (CTA) after doses of 0, 1.0, or 2.5 g/kg ethanol, and patterns of neuronal activation in response to ethanol using Fos-like immunohistochemistry (Fos+) to uncover regions where age differences in activation are associated with ethanol aversion. An adolescent-specific ethanol-induced increase in Fos+ staining was seen within the nucleus accumbens shell and core. An age difference was also noted within the Edinger-Westphal nucleus (EW) following administration of the lower dose of ethanol, with 1 g/kg ethanol producing CTA in adults but not in adolescents and inducing a greater EW Fos response in adults than adolescents. Regression analysis revealed that greater numbers of Fos+ neurons within the EW and insula (Ins) were related to lower consumption of the conditioned stimulus (CS) on test day (reflecting greater CTA). Some regionally specific age differences in Fos+ were noted under baseline conditions, with adolescents displaying fewer Fos+ neurons than adults within the prelimbic (PrL) cortex, but more than adults in the bed nucleus of the stria terminalis (BNST). In the BNST (but not PrL), ethanol-induced increases in Fos-immunoreactivity (IR) were evident at both ages. Increased ethanol-induced activity within critical appetitive brain regions (NAc core and shell) supports a role for greater reward-related activation during adolescence, possibly along with attenuated responsiveness to ethanol in EW and Ins in the age-typical resistance of adolescents to the aversive properties of ethanol.