There has been growing interest in using N-methyl-D-aspartate (NMDA) receptor antagonists as treatments for mood disorders, but there is still much to learn about their cognitive effects. Research shows NMDA receptors can affect decision-making, and the antagonist MK-801 has had varying effects in rodents. Specifically, some have reported impairments in working memory while foraging behaviors remained intact, while others have demonstrated changes in choice behavior related to delay or risk in behavior tasks. We investigated the role of NMDA receptors in the specific paradigm of optimal decision-making to further confirm MK-801’s effects and to explore whether inhibiting NMDA receptors alters optimal decision-making processes. To accomplish this, we used the Diminishing Returns task, in which rats were placed in a chamber containing two levers that returned rewards after delays. One lever had a fixed delay (FD) returning a reward after 10 s. The other lever had a progressive delay (PD) that increased by 1 s after each press. The task included two conditions allowing rats to change the delay schedule: no-reset and reset. In both conditions, there was an optimal response rate that returned the most rewards at the least amount of delay. A total of 24 male and female Sprague-Dawley rats were injected with doses of MK-801 (0.06 mg/kg, 0.1 mg/kg, 0.2 mg/kg) and saline as the control before testing in the task. We hypothesized MK-801 would diminish the ability to make optimal decisions. In the no-reset condition, rats on the 0.2 mg/kg dose made significantly more choices for the PD lever compared to the other treatments (56.9% ± 4.8%). In the reset condition, females made significantly more PD lever presses than males after receiving saline (females: 93.8% ± 1.1%, males: 88.7% ± 1.8%). Also, males and females on the 0.2 mg/kg dose made more optimal sequences of choices (females: 3.38 ± 0.87, males: 6.48 ± 1.67). These results reveal complex effects of sex and NMDA receptors on optimal foraging behaviors and overall task responsiveness. Therefore, the findings suggest inhibiting NMDA receptors may not detrimentally affect the cognitive mechanisms involved in optimal decision-making as it is measured in this task
