Differential patterns of alcohol and nicotine intake: Combined alcohol and nicotine binge consumption behaviors in mice

Abstract

Late adolescence and young adulthood, corresponding to the high school and college years, are vulnerable periods for increased alcohol and nicotine use. The dramatic increase in the prevalence of electronic cigarette use is particularly concerning in these age groups. Late adolescents and young adults are more likely to engage in cycles of binge drug consumption, and alcohol and nicotine are frequently used together. However, there are few data examining the combination of alcohol and nicotine in binge models in animal models. In this study, our objectives were to determine how voluntary nicotine consumption beginning in late adolescence influenced subsequent binge alcohol consumption in young adulthood, how a combination of alcohol and nicotine binge consumption differed from alcohol-only binge consumption, and whether nicotine would be consumed when presented in a binge procedure. Male C57BL/6J mice voluntarily consumed unsweetened alcohol and nicotine in continuous-access bottle-choice procedures in combination with cycles of drinking-in-the-dark. Our results show that experience with voluntary nicotine consumption in late adolescence did not affect subsequent binge alcohol consumption in early adulthood. However, mice that consumed nicotine in adolescence showed an initial decrease in alcohol preference, and consequently increase in nicotine preference, on the first session of combined ethanol and nicotine binge consumption in adulthood compared with mice that drank only water during late adolescence. Lastly, we found that mice readily consumed unsweetened nicotine when presented in a binge procedure, and the level of consumption exceeded the nicotine consumption observed in the combination alcohol and nicotine binge. Our data show that expansion of the patterns of alcohol and nicotine co-consumption in a mouse models is possible, which will enable us to dissect relevant molecular targets underlying these consumption patterns and better inform drug development efforts.

Keywords: Adolescent; Binge; Ethanol; Mice; Nicotine.

Figure 1.. Experimental outline.

Schematic timeline for the 5 groups.

Figure 2.. Two-bottle choice nicotine consumption and preference.

(A) The average nicotine consumption (mg/kg/day) and (B) nicotine preference in the N2BC EDID and N2BC Co-DID groups for the 5-week experiment. The weeks in which the 3-day binge consumption procedure occurred are outlined. There was a main effect of time for nicotine consumption and preference using 2-way RM ANOVAs. Data are presented as mean ± SEM, n=8 mice per group.

Figure 3.. Consumption of ethanol during ethanol-only binge and combination ethanol+nicotine binge.

Ethanol consumption in a binge procedure was unaffected by co-presentation of nicotine or by experience with voluntary nicotine consumption. (A) The average ethanol consumption during the 4h binge sessions for Weeks 3–5 (W3–5). *P<0.05, **P<0.01 using Tukey’s multiple comparisons test. (B) The average ethanol consumption during the 3-day binge procedure collapsed across the 3 weeks. Data are presented as mean ± SEM, n=8 mice per group for N2BC EDID, N2BC Co-DID and Co-DID groups, n=7 for EDID group.

Figure 4.. Consumption of nicotine during nicotine-only binge and combination ethanol+nicotine binge.

(A) The average nicotine consumption during the 4h binge sessions for Weeks 3–5 (W3–5). Nicotine consumption in a binge procedure was higher when nicotine was presented alone than when co-presented with ethanol. (B) The average nicotine consumption during the 3-day binge procedure collapsed across the 3 weeks. **P<0.01 compared with the Co-DID group, and ***P<0.001 compared with both the Co-DID and N2BC Co-DID groups within Day by Tukey’s multiple comparisons test. All groups consumed more nicotine during the 4h access on Day 3 (D3) compared to 2h access on Days 1 and 2. ^xxP<0.01, ^xxxxP<0.001 compared with nicotine consumption on Days 1 and 2 within group. Data are presented as mean ± SEM, n=8 mice per group.

Figure 5.. Voluntary nicotine consumption increases nicotine preference during a combination ethanol+nicotine binge.

The ethanol and nicotine preference during each session of the 3-day binge procedure over 3 weeks. Ethanol preference was lower, and therefore nicotine preference was higher, in the N2BC Co-DID group compared with the Co-DID group for Day 1 of Week 1. **P=0.03 compared with Co-DID group for the same day using Sidak’s multiple comparisons test. Data are presented as mean ± SEM, n=8 mice per group.