Poor attentional control as a sex-specific biomarker to assess vulnerability to nicotine addiction in mice

Every day thousands of people smoke a first cigarette, exposing themselves to the risk of becoming addicts. But this risk is not equal from individual to individual, inviting the hypothesis of potential biomarkers for predicting baseline vulnerability to addiction. One property of nicotine is to increase attentional capacities. However, the role of this pro-cognitive nicotinic effect in initiation of habitual smoking is unknown. Here, we investigated whether the differential effects of nicotine on cognitive performance in mice were predictive of sensitivity to nicotine reward and, if so, whether this characteristic was sex dependent. Naive populations of male and female mice were first assessed for their attentional performances in the attentional cued-Fixed-Consecutive-Number task (FCNcue) in baseline conditions and after nicotine injections (0.15 and 0.30 mg/kg). Next, all mice underwent nicotine-induced conditioned place preference (CPP) in order to evaluate inter-individual differences in nicotine (0.30 mg/kg) reward sensitivity. Our results showed that innately impulsive males, but not females, benefited from the pro-cognitive effect of nicotine and were also subsequently more sensitive to nicotine reward, indicating increased vulnerability to developing nicotine addiction. Females displayed a completely different behavioural pattern, whereby nicotine reward sensitivity was independent of baseline attentional performances. These results suggest that the pro-cognitive effect of nicotine plays a key role in the development of nicotine addiction in males but not females. Moreover, they signal that the cognitive processes and neurobiology underpinning innate impulsivity may differ significantly between males and females.