Developed as a tool to assess working memory capacity in rodents, the odor span task (OST) has significant potential to advance drug discovery in animal models of psychiatric disorders. Prior investigations indicate OST performance is impaired by systemic administration of N-methyl-D-aspartate receptor (NMDA-r) antagonists and is sensitive to cholinergic manipulations. The present study sought to determine whether an impairment in OST performance can be produced by systemic administration of the competitive NMDA-r antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP; 3, 10, 17 mg/kg i.p.) in a unique dual-component variant of the OST, and whether this impairment is ameliorated by nicotine (0.75 mg/kg i.p.). Male Sprague-Dawley rats were trained to asymptotic level of performance on a 24-trial two-comparison incrementing nonmatching to sample OST. In addition, rats were administered a two-comparison olfactory reference memory (RM) task, which was integrated into the OST. The RM task provided an assessment of the effects of drug administration on global behavioral measures, long-term memory and motivation. Several measures of working memory (span, longest run, and accuracy) were dose dependently impaired by CPP without adversely affecting RM. Analysis of drug effects across trial blocks demonstrated a significant impairment of performance even at low memory loads, suggesting a CPP-induced deficit of olfactory short-term memory that is not load-dependent. Although nicotine did not ameliorate CPP-induced impairments in span or accuracy, it did block the impairment in longest run produced by the 10 mg/kg dose of CPP. Overall, our results indicate that performance in our 24 odor two-comparison OST is capacity dependent and that CPP impaired OST working, but not reference, memory.The odor span task, which was originally developed by Dudchenko et al. (2000), makes use of a primary sensory modality for rodents (olfaction) to assess the neurobiological and neuropharmacological basis of rodent memory. In the original procedure, rats were trained to dig in cups of sand, each mixed with a different household spice (e.g., basil or paprika), to retrieve buried food rewards. On each successive trial, a novel odor was presented, along with every odor that had been presented in preceding trials, but only responses to the novel odor were reinforced. To respond accurately on any given trial the rat needed to remember each stimulus it had encountered earlier in the session and withholds responses to these stimuli. Therefore, memory demands escalated over the course of the procedure as the number of odors the rat was required to remember increased. Dudchenko et al. (2000) demonstrated that performance in the task declined across trials, indicating that task accuracy was negatively impacted by increasing memory load. However, in this OST procedure, the number of comparisons presented on each successive trial increases in tandem with the number of stimuli to remember, confounding the relationship between accuracy and mem...
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