A study of a topiramate pre-treatment on the effects induced by a subanaesthetic dose of ketamine on human reaction time

Ketamine, a N-methyl- d-aspartate (NMDA) receptor antagonist, impairs reaction time performance and interacts with foreperiod duration, thereby suggesting that ketamine alters motor preparation. These effects can be attributed either to the blockade of NMDA receptors or to the stimulation of α-amino-3-hydroxy-5-methylisoxasole-4-proprionic acid (AMPA) and kainate receptors. The purpose of the present study was: (i) to replicate previous findings and (ii) to study the effect of a pre-treatment with topiramate, an AMPA/kainate antagonist, on the impairments induced by ketamine on RT. Thirty six healthy subjects (3 groups of 12) performed a two-choice RT task in which the foreperiod was manipulated. All subjects performed the task under perfusion of ketamine (intravenous bolus of 0.12 mg followed by a perfusion of 0.5 mg/kg over 60 mn) or placebo (saline). Depending on the group, an oral dose of topiramate (50 mg) or placebo (lactose) was administered 2 h before ketamine infusion (randomised, double-blind, double-dummy, parallel-group design). At the dose studied, topiramate exerted no detectable effect on RT. The results relative to ketamine corroborate previous findings and suggest that this molecule affects motor preparation through the blockade of NMDA receptors.