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 that 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 weeks) and adult (10 weeks) male C57BL/6J mice for 2 to 4 h/d for 16 days. 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 the 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 kilogram 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.

Keywords: Development; binge; correlated trait; drinking; ethanol.

Figure 1. Adolescent C57BL/6J mice consume significantly more alcohol, per kg body weight, than adult mice in a limited-access paradigm

Adolescent and adult mice were presented with a 20% v/v alcohol solution in place of water for 2-h (days 1-3, 5-7, 9-11, and 13-15) or 4-h (days 4, 8, 12, and 16) per day, and intake was recorded. Shown are mean ± SEM values. (A) Analysis of alcohol intake over the twelve 2-h binge sessions revealed an increase in dose consumed in adolescents, as compared to adults, on days 2, 5, 9 and 10. (B) Analysis of alcohol intake during the 4-h binge sessions revealed a significant increase in alcohol consumption on day 12 (relative to day 4) in adolescents, but a significant decrease in alcohol consumption on day 16 (relative to day 4) in adults. The two age groups differed in alcohol intake on days 8, 12, and 16. (C) BACs, taken immediately following the final binge session on day 16, were significantly higher in adolescents as compared to adults. + significant difference from adults, ps<0.01. * significant difference from day 4 in the respective age group, ps<0.05.

Figure 2. Adolescent mice are less sensitive to the aversive properties of alcohol as compared to adult mice

During the conditioning phase of the experiment (Trials 1-5), mice were presented with the CS (0.2M NaCl) for 1-h/day; on conditioning trials 1-4, this 1-h access was immediately followed by an IP injection of saline or alcohol (3 or 4 g/kg). No alcohol treatment followed trial 5. Extinction of the conditioned response was assessed once every 5 d for 3 trials (6-8). Shown are mean ± SEM values. (A) In adolescent mice, only the 4 g/kg alcohol dose induced a conditioned taste aversion (CTA), and this aversion diminished after three extinction trials. In adults, however, both doses of alcohol (3 and 4 g/kg) produced a significant taste aversion, and a reduction of this aversion was only observed in adult mice treated with 3 g/kg alcohol prior to extinction. * significant difference from conditioning trial 1 (ps<0.05). ** significant difference from trial 6 (extinction) (ps<0.05). + significant difference from adolescents at the same alcohol dose and conditioning trial (ps<0.05). The dashed line represents no change from trial 1. (B) Shown in this figure is a summary of the change in CS consumption after conditioning (‘Conditioning Summary’, Trial 5 – Trial 1, the same data as plotted for Trial 5 in Fig. 2A) and the overall change in CS intake following 3 extinction trials (‘Extinction Summary’, Trial 8 – Trial 5). These data are re-graphed to emphasize the age difference in sensitivity to a CTA and in extinction of a CTA. Adult mice were more sensitive to the aversive effects of 3 g/kg alcohol as compared to adolescent mice (+ p<0.05), but did not differ from adolescents after 4 g/kg alcohol. Following 15 d of extinction, adolescent mice in the 4 g/kg alcohol group increased CS intake (indicative of extinction), but adult mice did not. Rather, an extinction of aversion was only observed in adult mice at a 3 g/kg alcohol dose (* p<0.05 as compared to the 0 g/kg group in the respective age group). Adolescent and adult mice differed significantly in the change in CS intake over extinction trials at both the 3 and 4 g/kg alcohol doses (+ p<0.05 at respective alcohol dose).