DOES KETAMINE-MEDIATED N-METHYL-D-ASPARTATE RECEPTOR ANTAGONISM CAUSESCHIZOPHRENIA-LIKE OCULOMOTOR ABNORMALITIES

Evidence from histological and pharmacological challenge studies indic ates that N-methyl-D-aspartate (NMDA) receptor hypofunction may play a n important role in the pathophysiology of schizophrenia. Our goal was to characterize effects of NMDA hypofunction further, as related to s chizophrenia-associated neuropsychological impairment. We administered progressively higher doses of ketamine (target plasma concentrations of 50, 100, 150, and 200 ng/ml) to 10 psychiatrically healthy young me n in a randomized, single-blind, placebo-controlled design and assesse d oculomotor, cognitive, and symptomatic changes. Mean ketamine plasma concentrations approximated target plasma concentrations at each infu sion step. Verbal recall, recognition memory, verbal fluency, pursuit tracking, visually guided saccades, and fixation all deteriorated sign ificantly during ketamine infusion; lateral gaze nystagmus explained s ome, but not all, of the smooth pursuit abnormalities. We concluded th at ketamine induces changes in recall and recognition memory and verba l fluency reminiscent of schizophreniform psychosis. During smooth pur suit eye tracking, ketamine induces nystagmus as well as abnormalities characteristic of schizophrenia. These findings help delineate the si milarities and differences between schizophreniform and NMDA-blockade- induced cognitive and oculomotor abnormalities. [Neuropsychopharmacolo gy 19:434-444, 1998] (C) 1998 American College of Neuropsychopharmacol ogy. Published by Elsevier Science Inc.