Behavioral pharmacology of the odor span task: Effects of flunitrazepam, ketamine, methamphetamine and methylphenidate.

The Odor Span Task is an incrementing non-matching-to-sample procedure that permits the study of behavior under the control of multiple stimuli. Rats are exposed to a series of odor stimuli and selection of new stimuli is reinforced. Successful performance thus requires remembering which stimuli have previously been presented during a given session. This procedure has been frequently used in neurobiological studies as a rodent model of working memory; however, only a few studies have examined the effects of drugs on performance in this task. The present experiments explored the behavioral pharmacology of a modified version of the Odor Span Task by determining the effects of stimulant drugs methylphenidate and methamphetamine, NMDA antagonist ketamine, and positive GABAA modulator flunitrazepam. All four drugs produced dose-dependent impairment of performances on the Odor Span Task, but for methylphenidate and methamphetamine, these occurred only at doses that had similar effects on performance of a simple odor discrimination. Generally, these disruptions were based on omission of responding at the effective doses. The effects of ketamine and flunitrazepam were more selective in some rats. That is, some rats tested under flunitrazepam and ketamine showed decreases in accuracy on the Odor Span Task at doses that did not affect simple discrimination performance. These selective effects indicate disruption of within-session stimulus control. Overall, these findings support the potential of the Odor Span Task as a baseline for the behavioral pharmacological analysis of remembering.