Elsevier

Biological Psychiatry

Volume 57, Issue 4, 15 February 2005, Pages 366-372
Biological Psychiatry

Original articles
Ketamine-induced distractibility: An oculomotor study in monkeys

https://doi.org/10.1016/j.biopsych.2004.10.036Get rights and content

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Section snippets

Subjects

Two male green monkeys (Caercopitheca aethiops, subjects V and K) served as subjects. The monkeys were kept in individual primate cages in an air-conditioned room. They weighed 4.5–5 kg and were given monkey chow ad libitum, supplemented daily with fresh fruit. The animals were water deprived during the day preceding the recording session. After the experiment, extra water was given if necessary. The experiments were performed while the monkey’s head was fixed and the eye movements were

Visually guided saccade task

Ketamine induced a significant increase of visually guided saccade latency in both monkeys, as shown in Table 1. Although there was no clear dose-effect relationship, no effect was observed in monkey V at .2 mg/kg, and higher doses tended to induce a greater increase than smaller doses. Saccade latency returned to the saline level in monkey K at the last trial, whereas it remained slightly increased in monkey V. Ketamine had a slightly different effect on saccade accuracy in our two monkeys:

Discussion

A large number of studies have shown that ketamine is a useful research tool for pharmacological studies on schizophrenia in humans (Lahti et al 1995). Previous studies on ketamine-induced oculomotor abnormalities have mainly found smooth pursuit impairments (Radant et al 1998; Weiler et al 2000; Avila et al 2002). However, this model has been incompletely validated, since the ability of ketamine to induce increased distractibility, such as seen in most schizophrenic subjects, has not been

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