Ketamine-induced distractibility: An oculomotor study in monkeys

Abstract

Administration of subanesthetic doses of ketamine, a noncompetitive N-methyl-D-aspartate receptor antagonist, induces a spectrum of behavioral disorders that are commonly observed in patients with schizophrenia. Although it has been demonstrated that poor antisaccade performance is a core dysfunction in schizophrenia, the ability of ketamine to induce an increased distractibility has not been demonstrated. The present study aimed to determine whether ketamine administration would reproduce the same antisaccade deficit as that observed in schizophrenic subjects. We studied the effect of acute ketamine or saline administration on the performance of two monkeys trained on a reflexive visually guided saccade task and an antisaccade task. The main result is that ketamine administration induced a markedly increased antisaccade error rate and increased antisaccade latency, similar to that seen in schizophrenic subjects. Other impairments consisted of increased reflexive saccade latency and the presence of a gaze-evoked nystagmus. This study supports the validity of ketamine as a pharmacological model of schizophrenia. Based on the known pharmacological effects of ketamine, further studies should allow the investigation of the pharmacological basis of distractibility.