255. - Oculomotor. Cognitive and subjective effects of ketamine in normals

Abstract

Reduced glutamate receptors in posr-monern studies of schizophrenics and the induction of positive and negative symptoms by non-competitive NMDA antagonists in normals suggesta role for the NMDA receptor in psychotic illness. To further explore thls, we sought to determine if subunesihetlc doses of ketarnine induced oculomotor abnonnalities typical of schizophrenia in normal controls. Ten psychiatrically healthy subjects received infusions ofeither ketamine at 5 increasing blood levels for 30 minutes each (0,5,10,15,20 jJ.g!ml) or placebo (single blind) on two separate days. Ocutomotor, and memory tasks, verbal fluency, and visual analog ratings were obtained at each dose and analyzed with repeated measures ANOVAs (drug vs, placebo X infusion step), The smooth pursuit measures gain, catch up, intrusive, and total saccade frequency (but not anticipatory saccade frequency), all deteriorated significantly on ketamlne infusion (p uggt:!>ts that they may reflect ketarnlne induced brain dysfunction more accurately limn other measures. Although some aspects of the oculomotor dysfunctions are characteristic of schizophrenia, the nystagmus observed during luternl Iixtltion suggests that kctnmlne rnuy Induce some other phenomenon Ihul grossly mimics schizophrenic smooth pursuit but has a different rnechnnlsm,