Effects of Nicotine on a Translational Model of Working Memory

Cognitive research with human non-smokers has demonstrated that nicotine generally enhances performance on tasks of attention but, working memory does not appear to be affected. In contrast, nicotine has been shown to produce robust enhancements of working memory in non-human animals. To address this disparity, the present study investigated the effects of nicotine (2mg, 4mg nicotine gum, and placebo) on the performance of 30 non-smokers (15 male) completing a working memory task developed for rodents (the odor span task, OST). Nicotine has been reported to enhance OST performance in rodents and the present study sought to determine whether the effect is generalizable to human performance. In addition to completing the OST, participants completed a cognitive battery of clinical and experimental tasks assessing working memory and attention. This allowed for a direct comparison of OST performance to other commonly used measures of human cognition. Findings showed that nicotine was associated with dose dependent enhancements in sustained attention, as evidenced by increased hit accuracy on the rapid visual information processing (RVIP) task. However, nicotine failed to produce main effects on OST performance or on alternative measures of working memory (digit span, spatial span, letter-number sequencing, 2-back) or attention (digits forward, 0-back). Interestingly, enhancement of RVIP performance occurred concomitant to significant reductions in self-reported attention/concentration. Human OST performance was significantly related to Nback performance and, as in rodents, OST accuracy declined with increasing memory load. Given the similarity of human and rodent OST performance and the strong association observed vi between OST and visual 0-back accuracy, the OST may be particular useful for preclinical studies of conditions characterized by inattention.