Adolescent C57BL/6J Mice Show Elevated Alcohol Intake, but Reduced Taste Aversion, as Compared to Adult Mice: A Potential Behavioral Mechanism for Binge Drinking

Abstract

Background Binge alcohol drinking during adolescence is a serious health problem which may increase future risk of an alcohol use disorder. Although there are several different procedures by which to preclinically model binge-like alcohol intake, limited-access procedures offer the advantage of achieving high voluntary alcohol intake and pharmacologically relevant blood alcohol concentrations (BACs). Therefore, in the current study, developmental differences in binge-like alcohol drinking using a limited-access cycling procedure were examined. In addition, as alcohol drinking has been negatively correlated with sensitivity to the aversive properties of alcohol, we examined developmental differences in sensitivity to an alcohol-induced conditioned taste aversion (CTA). Methods Binge-like alcohol consumption was investigated in adolescent (4 wk) and adult (10 wk) male C57BL/6J mice for 2-4 h/day for 16 d. Developmental differences in sensitivity to an alcohol-induced CTA were examined in adolescent and adult mice, with saline or alcohol (3 or 4 g/kg) repeatedly paired with intake of a novel tastant (NaCl). Results Adolescent mice showed a significant increase in alcohol intake as compared to adults, with adolescents achieving higher BACs and increasing alcohol consumption over successive cycles of the binge procedure. Conversely, adolescent mice exhibited a dose-dependent reduction in sensitivity to the aversive properties of alcohol, as compared to adult mice, with adolescent mice failing to develop a CTA to 3 g/kg alcohol. Finally, extinction of an alcohol CTA was observed following conditioning with a higher dose of alcohol in adolescent, versus adult, mice. Conclusions These results indicate that adolescent mice consume more alcohol, per kg body weight, than adults in a binge-like model of alcohol drinking, and demonstrate a blunted sensitivity to the conditioned aversive effects of alcohol. Overall, this supports a behavioral framework by which heightened binge alcohol intake during adolescence occurs, in part, via a reduced sensitivity to the aversive properties of alcohol.

Involvement of the GABAA Receptor in Age‐Dependent Differences in Binge‐Like Ethanol Intake

“…This effect was robust and reliable, as higher EtOH intakes in adolescents were observed in both experiments, and is in agreement with all other drinking studies using limited-access procedures (Bell et al, 2011;Holstein et al, 2011;Moore et al, 2010). Although polydipsia (Bell et al, 2011), hyperphagia (Spear, 2000), or higher social isolation stress (Lopez et al, 2011) in adolescents could contribute to these results, we think these explanations were unlikely.…”

Use of the light/dark test for anxiety in adult and adolescent male rats

“…Adolescent rats exhibited more approach behavior and less risk assessment in a novel, aversive environment and were less sensitive to the anxiogenic effects of FG-7142 and yohimbine. In addition to the reduced anxiogenic effects of multiple drugs in adolescent rats in the LD test, adolescents are less sensitive than adults to the aversive effects of many drugs in the conditioned taste aversion paradigm [20,21,62–68,69,70]. Adolescent rats also have a deficit in expression of conditioned fear despite being able to retain the fear memory and express a normal freezing reaction in adulthood [71].…”

The ontogeny of ethanol aversion

“…While there is convincing evidence from both our laboratory and others that mid-adolescents are less sensitive to CTA to ethanol than are adults (Anderson et al, 2010; Holstein, Spanos, & Hodge, 2011; Schramm-Sapyta et al, 2010; C. Vetter-O’Hagen et al, 2009), the precise ontogeny of these aversive properties has yet to be identified.…”