We must look beyond primary reinforcement to understand nicotine use in women

Women exhibit greater nicotine use vulnerability than men. Common cessation treatments are less effective for women, suggesting unique contributors to women's smoking that are not fully characterized or targeted by available treatments. High estradiol is associated with enhanced smoking and cessation difficulty, whereas high progesterone is associated with reduced smoking and better cessation success. Hormonal contraceptives can produce similar or even outsized alterations in nicotine use outcomes. Despite clear effects of natural and synthetic sex steroid hormones on nicotine intake, the behavioral pathways by which hormones alter nicotine use outcomes remain unmapped. In this review paper, we propose that uncovering such mechanisms requires examining sex steroid hormone modulation of non-primary reinforcement factors in our animal models. Parallel effects of natural and synthetic sex steroid hormones on nicotine self-administration occur in animal models. Further, women's smoking is more influenced by environmental stimuli, such as the smell, taste, and visual cues associated with nicotine use than by the reinforcing effects of nicotine. In building our case, we first summarize research supporting the import of environmental factors in nicotine intake for women and translation to female rats. We also synthesize findings on how biological sex and sex steroid hormones influence these mechanisms in humans and rats. Lastly, we will detail promising directions for future research.