Adolescent C57BL/6J (but not DBA/2J) mice consume greater amounts of limited-access ethanol compared to adults and display continued elevated ethanol intake into adulthood

Abstract

Background: Alcohol use is common during the adolescent period, a time at which a number of crucial neurobiological, hormonal, and behavioral changes occur (Spear, 2000). In order to more fully understand the complex interaction between alcohol use and these age-typical neurobiological changes, animal models must be utilized. Rodents experience a developmental period similar to that of adolescence. Although rat models have shown striking adolescent-specific differences in sensitivity to ethanol, little work has been done in mice despite the fact that the C57BL/6J (B6) and DBA2/J (D2) mice have been shown to markedly differ in ethanol preference drinking and exhibit widely different sensitivities to ethanol.

Methods: The current study examined ethanol intake in adolescent and adult B6 and D2 mice using a limited access alcohol exposure paradigm called Drinking in the Dark (DID). Additionally, the effect of adolescent (or adult) ethanol exposure on subsequent adult ethanol intake was examined by re-exposing the mice to the same paradigm once the adolescents reached adulthood. We hypothesized that adolescent (P25-45) mice would exhibit greater binge-like alcohol intake compared to adults (P60-80), and that B6 mice would exhibit greater binge-like alcohol intake compared to D2 mice. Moreover, we predicted that relative difference in binge-like alcohol intake between adolescents and adults would be greater in D2 mice.

Results: Adolescent B6 mice consumed more ethanol than adults in the DID model. There was no difference between adolescent and adult D2 mice.

Conclusions: This work adds to the literature suggesting that adolescents will consume more ethanol than adults and that this exposure can result in altered adult intake. However, this effect seems largely dependent upon genotype. Future work will continue to examine age-related differences in ethanol intake, preference, and sensitivity in inbred mouse strains.

Fig. 1

Ethanol intake. Note that there was a 3-week abstinence period between experimental phases 1 and 2. B6 adolescent mice consumed more ethanol than their adult counterparts upon initial exposure (p < 0.001), and exposure to ethanol during adolescence resulted in increased ethanol intake during adulthood (p < 0.01; A,B). There was no difference among D2 adolescents and adults in ethanol intake, nor did adolescent ethanol exposure alter subsequent adult ethanol intake in D2 mice (C,D). Asterisks (**p < 0.01; p < 0.001) indicate significant differences among adolescents and adults within an experimental phase. Number signs (#p < 0.001) indicate significant differences among adults (P63–76) with prior adolescent ethanol exposure and adults (P63–76) with no prior ethanol exposure.

Fig. 2

Pattern of ethanol intake. Note that there was a 3-week abstinence period between experimental phases 1 and 2. Ethanol Exposure Day 1: No specific differences in the pattern of ethanol intake emerged among B6 and D2 or adult and adolescent mice (A). Ethanol Exposure Day 7: B6 mice consumed most of their fluid during the first 30 minutes of ethanol access (p’s < 0.03), while no differences in intake patterns emerged in the D2 mice (B). Ethanol Exposure Day 14: Again, B6 mice consumed most of their fluid during the first 30 minutes of ethanol access (p’s < 0.001), and there was no difference between B6 and D2 ethanol intakes in the 3rd and 4th 30-minute access periods (C). Ethanol Exposure Day 15: B6 mice that were previously exposed to ethanol as adolescents consumed most of their fluid in the first 30 minutes of ethanol access (p = 0.001), and no differences in patterns emerged in the B6 mice previously exposed as adults or in the D2 mice (D). Ethanol Exposure Day 21: B6 mice consumed most of their fluid during the first 30 minutes of ethanol access (p’s < 0.001), while no differences in intake patterns emerged in the D2 mice (E). Ethanol Exposure Day 28: B6 mice previously exposed to ethanol during adolescence consumed more than B6 mice previously exposed to ethanol during adulthood in the first 30 minutes of ethanol access (p < 0.001) while in the 2nd 30 minutes of ethanol access the opposite is true (p < 0.01; F).