A model of effects of ketamine, a NMDA glutamatergic antagonist, on executive control in monkeys G. Stoet and L.H. Snyder Anatomy and Neurobiology, Washington University in St.Louis, MO, USA Executive control is the mental capacity to plan, coordinate, and regulate how we respond to stimuli. The capacity to switch between different tasks is an important index of executive control commonly used in psychiatric tests. We studied an animal model of executive control. Monkeys performed trials of two visual discrimination tasks, which were randomly interleaved. On each trial, the monkey was presented a task cue, which informed him to perform either a color or a shape discrimination on the following stimulus. The animal responded with a left or right button press to the subsequent stimulus. We measured response time as a function of whether a trial followed the same task (repeat trial) or a different task (switch trial), and whether stimuli required a low or a high level of selective attention. Monkeys are not slower on switch trials, unless the intertrial interval (ITI) is extremely short. This is different from humans, who reliably show switch costs. Some human studies have reported that ketamine administration lengthens switch times. Although our data show a dose-related increase in reaction time, we found no specific impairment on the ability to switch between tasks. There are a number of differences between task-switching studies that report increased task-switching costs and ours. The animals in our study were highly trained before we measured the effect of ketamine on behavior. Another difference is methodological. Many of the human studies required subjects to use short-term memory to detect the occurrence and type of task switch (e.g., Wisconsin Card Sorting Task, WCST), while we directly instructed the task to be performed on each trial. Thus it is possible that the effect of ketamine on switch times in human studies was mediated by an effect on short-term memory and not on executive control per se. In conclusion, the capacity to switch between tasks is unaffected by ketamine in monkeys. Factors other than executive control might contribute to task switching problems in humans tested using WCST or a related paradigm. Finally, our results suggest that ketamine may be of limited use for understanding executive disorders in animal models.