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 N-back 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 between OST and visual 0-back accuracy, the OST may be particular useful for preclinical studies of conditions characterized by inattention.

Indiana University-Purdue University Indianapolis (IUPUI) / Posttraumatic stress disorder involves a constellation of neural and behavioral alterations in response to trauma exposure. Aside from symptoms involved in posttraumatic stress disorder diagnosis, patients frequently present with working memory impairments. Working memory training has been established as an effective intervention to reduce posttraumatic stress symptoms. Working memory is associated with posttraumatic stress disorder in that it is commonly impaired in patients and that training can reduce the severity of posttraumatic stress symptoms. Taken together, these points suggest the possibility of a shared mechanism between working memory and posttraumatic stress disorder but working memory has not been studied thoroughly in rodent models of posttraumatic stress disorder. The present study utilizes footshock trauma to induce a posttraumatic stress state in rats and evaluates the effect of trauma and trauma-paired cues on working memory performance. Results demonstrate the emergence of chronic deficits in working memory among traumatized animals three weeks post-trauma. Presentation of trauma-paired cues caused further decrement in working memory performance. Regression analysis indicates that the degree of working memory impairment in response to a trauma-paired cue can be significantly predicted by behavioral phenotypes typic of diagnostic symptoms for posttraumatic stress disorder. This study enhances existing animal models by replicating the clinical observations of working memory deficits associated with posttraumatic stress disorder. This will pave the way for future work to probe underlying mechanistic dysregulation of working memory following trauma exposure and for future development of novel treatment strategies.

<p>  </p> <p>Posttraumatic stress disorder involves a constellation of neural and behavioral alterations in response to trauma exposure. Aside from symptoms involved in posttraumatic stress disorder diagnosis, patients frequently present with working memory impairments. Working memory training has been established as an effective intervention to reduce posttraumatic stress symptoms. Working memory is associated with posttraumatic stress disorder in that it is commonly impaired in patients and that training can reduce the severity of posttraumatic stress symptoms. Taken together, these points suggest the possibility of a shared mechanism between working memory and posttraumatic stress disorder but working memory has not been studied thoroughly in rodent models of posttraumatic stress disorder. The present study utilizes footshock trauma to induce a posttraumatic stress state in rats and evaluates the effect of trauma and trauma-paired cues on working memory performance. Results demonstrate the emergence of chronic deficits in working memory among traumatized animals three weeks post-trauma. Presentation of trauma-paired cues caused further decrement in working memory performance. Regression analysis indicates that the degree of working memory impairment in response to a trauma-paired cue can be significantly predicted by behavioral phenotypes typic of diagnostic symptoms for posttraumatic stress disorder. This study enhances existing animal models by replicating the clinical observations of working memory deficits associated with posttraumatic stress disorder. This will pave the way for future work to probe underlying mechanistic dysregulation of working memory following trauma exposure and for future development of novel treatment strategies. </p>