The effects of a sub-anaesthetic dose of ketamine on human selective attention

A growing number of studies demonstrate that antagonists of the N-methyl-D- aspartate (NMDA) receptors can induce a broad range of psychophysiological anomalies in healthy subjects similar to those observed in schizophrenia. I n this study, the effect of a sub-anaesthetic dose of the non-competitive N MDA antagonist, ketamine, on human selective attention was explored. It was hypothesized that ketamine would induce in healthy subjects psychophysiolo gical anomalies that are commonly observed in schizophrenic patients, such as reduced P3000 amplitude and a reduction of both mismatch negativity (MMN ) and processing negativity (PN). In a double-blind randomized palcebo-cont rolled design, healthy male volunteers (n = 18) were challenged with a sub- anaesthetic dose of ketamine (0.3 mg/kg iv) after which they were tested in a selective attention task. In this task, two types of stimuli were evenly presented to the left or right ear; standard tones (80%) and deviant tones (20%) of either 1000 or 1100 Hz. The duration of a stimulus (95 dB) was 50 ms, the interstimulus intervals were randomized between 1750 and 2150 ms. The volunteer was instructed to push a button as quickly as possible after hearing the deviant tone in a specified ear. Ketamine did not alter perform ance of the subjects: in both the placebo and drug condition their reaction times for and percentages of hits and false alarms did not differ. Ketamin e did, however, reduce PN and the P300 amplitude (both in general and to de viant stimuli in particular). However, no drug effect on MMN was found. In addition, ketamine enhanced the N100 amplitude to deviant stimuli. In concl usion ketamine induces some of the attentional deficits in healthy controls that are observed in schizophrenic patients. Consequently, reduced glutama tergic activity in the brain may be involved in some of the symptoms of sch izophrenia. [Neuropsychopharmacology 22:293-302, 2000] (C) 2000 American Co llege of neuropsychopharmacology. Published by Elsevier Science Inc.