Clinical and preclinical evidence of sex differences in nicotine-induced enhancement of alcohol self-administration.

rationaleAlcohol and nicotine are frequently co-used, with significant implications for public health, particularly for women. Nicotine is known to enhance the response to other reinforcers in the immediate environment, including alcohol. Although many studies have examined the potential intersections of alcohol and nicotine use, few have directly examined any potential sex differences in the ability of nicotine to potentiate the reward and reinforcement of alcohol.

objectiveSummarize all extant evidence from clinical and preclinical studies that have investigated nicotine-induced enhancement of alcohol self-administration in male and/or female subjects, with a particular focus on studies that have directly assessed sex differences. METHODS AND

resultsWe obtained relevant studies from PubMed and GoogleScholar, selecting only studies in which alcohol self-administration occurred under the influence of passively-administered nicotine. We identified five clinical studies and 20 preclinical studies that matched our inclusion criteria, and only a subset of those studies directly examined male and female subjects. Although the collected evidence from these studies is limited, we discuss substantial evidence from other studies exhibiting sex differences in the neuropsychobiological mechanisms by which nicotine can modulate alcohol-related behaviors.

conclusionsBy highlighting the limited number of studies that have directly assessed sex differences in nicotine-induced enhancement of alcohol self-administration, we propose different avenues to address the gaps in the literature. Since rising rates of alcohol use disorder and nicotine-alcohol co-use disproportionately impact women, future research should prioritize mechanistic explorations and translational paradigms to tailor therapeutic strategies.