Sex differences in nicotine preference

Abstract

Smoking is the major cause of preventable deaths worldwide, and although there is a decline in overall smoking prevalence in developed countries, the decline in women is less pronounced than in men. Women become dependent faster and experience greater difficulties in quitting. Similar trends have been observed in animal models of nicotine/tobacco addiction. Individual differences in vulnerability to drug abuse are also observed in nicotine/ tobacco addiction and point to the importance of sex differences. This Review, summarizes findings from three experimental approaches used to depict nicotine preference in animal models, intravenous and oral nicotine selfadministration and nicotine-induced conditioned place preference. Nicotine preference is considered to be reflected in the animal's motivation to administer the drug (intravenously or orally) or to prefer an environment paired with the presence of the drug (conditioned place preference). These approaches all point to the importance of sex and age of the subjects; the preference of females and adolescents appear to be more pronounced than that of males and adults, respectively. A closer look at these factors will help us understand the mechanisms that underlie nicotine addiction and develop strategies to cope. Ignoring sex differences and reaching conclusions based only on studies using male subjects has resulted in erroneous generalizations in the past. Sex differences in nicotine preference have been clearly documented, and awareness on this aspect of nicotine dependence will significantly impact our success in translational research. V C 2016 Wiley Periodicals, Inc.

Variability in nicotine conditioned place preference and stress‐induced reinstatement in mice: Effects of sex, initial chamber preference, and guanfacine

“…*P < .05 primary reinforcer 6,7 with well-documented variability in the expression of nicotine reward-related behaviors. 13,[15][16][17][18]52,63,64 While previous studies have reported significant nicotine CPP acquisition with n ≤ 12, the small effect size in our study compared with others is likely because of a combination of strain differences 45,52 and the use of counterbalanced vs biased procedures, 65 as discussed further below.…”

“…The consistent acquisition scores across independently tested cohorts suggests the effect of nicotine is highly reproducible (Figure B,D). Nicotine is a relatively weak primary reinforcer with well‐documented variability in the expression of nicotine reward‐related behaviors . While previous studies have reported significant nicotine CPP acquisition with n ≤ 12, the small effect size in our study compared with others is likely because of a combination of strain differences and the use of counterbalanced vs biased procedures, as discussed further below.…”

“…Our study design produced a rich behavioral dataset in the various days on which CPP was measured and in the variability in preference scores. This variability in response to nicotine has been well documented . Our study further explored a potential source of variability with median split analyses based on pretest preference scores.…”

“…However, nicotine can also enhance the rewarding properties of nonpharmacological stimuli, enhance cognitive function, and interact with stress and anxiety to support addiction‐related behaviors. Interactions between these various effects of nicotine may account for the well‐documented interindividual variability in nicotine use and relapse observed in both human studies and rodent models . Further, individual differences may interact with sex to affect nicotine use.…”

“…Interactions between these various effects of nicotine may account for the well-documented interindividual variability in nicotine use and relapse observed in both human studies and rodent models. [13][14][15][16][17][18] Further, individual differences may interact with sex to affect nicotine use. For example, women are less sensitive to the primary reinforcing effects of nicotine than men, 19 but are more motivated by nicotine's effects on stress and negative affect.…”