A subanesthetic dose of ketamine in the Rhesus monkey reduces the occurrence of anticipatory saccades.

Rationale: It has been shown that antagonism of the glutamatergic N-methyl-D-aspartate (NMDA) receptor with subanesthetic doses of ketamine perturbs the perception of elapsed time. Anticipatory eye movements are based on an internal representation of elapsed time. Therefore, the occurrence of anticipatory saccades could be a particularly sensitive indicator of abnormal time perception due to NMDA receptors blockade.

Objectives: The objective of this study was to determine whether the occurrence of anticipatory saccades could be selectively altered by a subanesthetic dose of ketamine.

Methods: Three Rhesus monkeys were trained in a simple visually guided saccadic task with a variable delay. Monkeys were rewarded for making a visually guided saccade at the end of the delay. Premature anticipatory saccades to the future position of the eccentric target initiated before the end of the delay were not rewarded. A subanesthetic dose of ketamine (0.25 mg/kg) or a saline solution of the same volume was injected i.m. during the task.

Results: We found that the injected dose of ketamine did not induce sedation or abnormal behavior. However, in ∼4 min, ketamine induced a strong reduction of the occurrence of anticipatory saccades but did not reduce the occurrence of visually guided saccades.

Conclusion: This unexpected reduction of anticipatory saccade occurrence could be interpreted as resulting from an altered use of the perception of elapsed time during the delay period induced by NMDA receptors antagonism.