transferases br Methods br Results br Discussion The results

Methods
Results
Discussion The results of the current study demonstrate that regardless of whether adolescents were exposed to ethanol in early or late adolescence, animals that received binge-like exposure to alcohol during adolescence exhibited notable long-lasting attenuations in the aversive effects of ethanol relative to their counterparts that did not receive ethanol during adolescence. During testing shortly after the end of the exposure periods, this effect was more pronounced in late AIE animals, with these animals requiring a higher dose (2.5g/kg) than early AIE animals (2.0g/kg) to express ethanol CTA. This slight difference of exposure age failed to hold through to CTA-2, with both early and late AIE animals tested in adulthood not expressing CTA until the highest (2.5g/kg) dose—a dose notably higher than necessary to produce CTA in their control counterparts. Given that adolescent animals are normally less sensitive than adults to ethanol\'s aversive effects, as indexed via ethanol CTA (Anderson et al., 2010), these findings are reminiscent of other work showing that ethanol exposure during adolescence sometimes results in the retention of an adolescent-typical transferases into adulthood (see Spear and Swartzwelder, 2014, for a review). The differences in baseline intake prior to CTA-1 across the to-be-administered CTA dose conditions must reflect incidental variations associated with random assignment, given that treatment of these groups was identical prior to the baseline test. During the baseline intake sessions for CTA-1, however, the chronic water animals from both exposure ages were also found to consume more of the “supersac” solution used as the tastant than the other exposure groups. This effect of prior exposure condition could potentially reflect an effect of the presumably mild stress associated with repeated gavage, with ethanol-exposed animals perhaps not expressing similar increases due to anxiolytic effects of ethanol. Many studies examining the effects of stress during adolescence have investigated long-term differences, with mixed results often depending on stressor severity, rat strain, and sex (e.g. see McCormick and Green, 2013 for a review). In the few studies examining immediate effects of stress during adolescence, however, males were found to be relatively resistant to decreases in sucrose consumption (Bourke and Neigh, 2011; Ducci et al., 2009; Hong et al., 2012), with females sometimes even reported to show increased sucrose consumption following repeated mild stress (Bourke and Neigh, 2011; Pohl et al., 2007). Regardless of the factors contributing to this gavage effect seen with CTA-1, it did not persist until CTA-2. It is possible that by this test, sufficient time had elapsed for recovery from the potentially mild stress of gavage. Alternatively (and perhaps at least as likely), it is possible that the accentuated intake after repeated gavage may be restricted to sweet stimuli such as “supersac” and may not emerge with a non-sweet taste stimulus such as the salt solution used as the tastant in CTA-2. Test day intake during CTA-1 revealed that animals that received intermittent exposure to ethanol during adolescence exhibited attenuated sensitivity to the aversive properties of ethanol, with this insensitivity slightly more pronounced in late AIE animals. At testing in adulthood (CTA-2), however, comparable insensitivities were seen in AIE animals exposed at either of the two ages. These findings are consistent with previous studies also showing attenuated ethanol CTA after ethanol exposure in adolescence, despite notable differences in exposure mode [i.g. here vs. i.p. (Alaux-Cantin et al., 2013) and vapor exposure (Diaz-Granados and Graham, 2007)] in other studies. While the current data are in accordance with previous findings that early AIE results in attenuated CTA in adulthood, the similarity in findings with late AIE contrasts with that reported by Alaux-Cantin et al. (2013) using i.p. exposure. The age at which early and late exposures were administered differed only slightly between studies, with Alaux-Cantin and colleagues using P30-43 and P45-58 for early and late adolescence, respectively, whereas these groups were represented by P25-45 and P45-65 in the current study. Hence, it is likely that route of administration or other differences across labs may contribute to this and other differences reported between i.p. and i.g. routes with AIE data (e.g., compare results of i.p. (Alaux-Cantin et al., 2013) and i.g. (Broadwater et al., 2011) on later ethanol consumption). For a number of response measures, studies comparing early and late adolescent AIE exposure have observed that ethanol exposure beginning pre-pubertally and extending into puberty produce different consequences that those beginning later in adolescence (see Spear, 2015, in press), with early exposure often resulting in an extension of an adolescent-typical phenotype, and late exposure resulting in more adult-typical consequences. From these CTA data, it would appear that sensitivity to ethanol\'s aversive effects might be an exception, with exposure to ethanol throughout a broad range of adolescence sufficient to attenuate later sensitivity to ethanol aversion in a way that could serve to promote later intake.