N-methyl-D-aspartate receptor inhibition alters rodent optimal decision making in the diminishing returns task

N-methyl-D-aspartate (NMDA) receptor antagonists are increasingly used for treating mood disorders, but there is much to learn about their cognitive effects. Research shows NMDA receptor antagonists have varying effects in temporal decision making, either increasing or decreasing optimal choice behaviors related to impulsiveness and delay sensitivity. To clarify their role in these behaviors, we investigated the role of the NMDA receptor antagonist MK-801 in the diminishing returns designed to investigate the ability to delay immediate rewards to optimize total rewards per session. Male and female rats were given the option to choose either a fixed delay lever that returned reward after 10 s or a progressive delay lever that delivered reward with no initial delay but increased by 1 s after each press. The task included two conditions: no-reset where the progressive delay continues to increase and reset where the progressive delay resets to 0 s after an fixed delay press. Following training, rats were injected with MK-801 (0.06 mg/kg, 0.1 mg/kg, 0.2 mg/kg) or saline before a session. In the no-reset condition, rats on the high dose demonstrated impaired choice behavior characterized by frequent nontask related lever presses during delay periods. In the reset condition, males and females on the high dose made more optimal sequences of choices despite females increasing omitted trials. In both conditions, lever press behavior points to a loss of sensitivity to delay intervals driving the observed effects. Overall, results revealed complex effects of sex and NMDA receptor antagonists on optimal foraging behaviors and overall task responsiveness. (PsycInfo Database Record (c) 2026 APA, all rights reserved).