Effects of dizocilpine (MK801) on olfactory span in rats

NMDA receptor antagonists interfere with learning and memory in some tasks, but not others. Some recent accounts have suggested that tasks placing demands on working memory are those most likely to be affected, and the present study tested this hypothesis. The purpose of the study was to adapt a recently developed procedure designed to test working memory capacity, the olfactory memory span task, for use in behavioral pharmacology and to then determine the effects of the NMDA receptor antagonist, dizocilpine (MK801) on performance in this task. Rats were trained in a non-match-to-sample procedure under conditions in which they had to remember an increasing number of olfactory stimuli as the session progressed. Simple olfactory discrimination trials were interspersed to provide a performance control. Effects of dizocilpine (.03, .10, .17, .3 mg/kg) were determined after stable performances were obtained. Rats were able to sustain stable performances on both the span and simple discrimination tasks with average spans of about 10 items. Accuracy declined as the number of stimuli to remember increased, and dizocilpine impaired accuracy in a dose-dependent and memory-load dependent fashion. The finding that the effects of dizocilpine interacted with the number of stimuli to remember is generally consistent with hypotheses linking NMDA receptors and working memory processes.

Research highlights
► The olfactory span task was used as a measure of working memory in rodents.
► Accuracy decreased as the number of stimuli to remember increased.
► NMDA antagonist, dizocilpine (MK801) decreased accuracy at doses that did not interfere with other aspects of performance.
► Dizocilpine effects were more pronounced as the memory load increased.