Voluntary intermittent access to combined alcohol and nicotine in mice—consumption and withdrawal effects

The prevalence of alcohol and nicotine use is widely known, though the co-abuse of the two is often understudied. Studies have shown that nicotine dependence and daily nicotine consumption increase with higher levels of alcohol consumption1. Nicotine use has been shown to decrease the subjective effects of alcohol and increase alcohol craving. Previous studies using the intermittent access (IA) paradigm in C57BL/6J (B6) mice have shown that B6 mice readily increase or escalate consumption of alcohol in this paradigm. Still, there is little information on alcohol and nicotine co-consumption and withdrawal using the IA paradigm. The goal of this study was to investigate the use of the IA paradigm for nicotine consumption, preference, and withdrawal, both alone and in combination with alcohol. It was hypothesized that the combination of alcohol and nicotine would lead to increased consumption and worsened withdrawal outcomes. This experiment used B6 mice (n=32, 16 females, 16 males) that were given intermittent 24-hour access to the experimental bottles over 4 weeks. There were 4 experimental groups: water (control), alcohol only (5% v/v), nicotine only (30 μg/mL), and alcohol and nicotine (5% v/v and 30 μg/mL). The concentrations of alcohol and nicotine were held consistent throughout the 4 weeks. Consumption and preference data were analyzed via a series of 2 (sex: male vs. female) x 4 (week) mixed factor ANOVAs. Open Field Test (OFT) was used to examine anxiety-like withdrawal behavior approximately 6 hours after the removal of the experimental bottles following the 4 weeks. Results showed a significantly higher consumption of and preference ratio for the combination of alcohol+nicotine compared to nicotine alone in both male and female mice. The OFT showed that female mice in the nicotine-only group spent significantly more time freezing compared to either group that received alcohol, which could be indicative of anxiety-like withdrawal behaviors. Studies such as this one that examine the co-consumption of two commonly abused drugs are crucial in improving our understanding of substance dependence as well as withdrawal.