The Effects of Combined Alcohol and Nicotine in a Two-bottle Choice Paradigm in C57BL/6J Mice

Alcohol and nicotine are both very commonly abused and are also widely abused in combination with one another. Smoking tobacco cigarettes has been shown to increase the number of alcoholic drinks per day and increase the chances of alcohol dependence. As both substances are known to individually elevate dopamine levels in the mesocorticolimbic reward system and also activate the hypothalamic-pituitary-adrenal (HPA) axis to release stress hormones known as glucocorticoids, including corticosterone in rodents. Using a two-bottle choice paradigm, we investigated the effects of the acquisition, maintenance, and withdrawal from chronic, combined alcohol (5-20% v/v) and nicotine (10-40 μg/ml) in male and female C57BL/6J mice. Withdrawal behavior and plasma corticosterone levels were measured approximately 18 hours after alcohol and nicotine were both removed. Mice exposed to alcohol, nicotine, or the combination of alcohol and nicotine exhibited slightly elevated anxiety-like behavior as evidenced by increased number of marbles buried during the withdrawal period compared to water controls in the marble burying task. All mice tested including those exposed to alcohol and/or nicotine had elevated levels of the rodent stress hormone corticosterone during the withdrawal period compared to basal corticosterone levels taken before any nicotine or alcohol exposure. Given the large number of individuals who are co-dependent on both alcohol and nicotine, future studies should continue to examine the effects of combined alcohol and nicotine