Clinical and sensorimotor gating effects of ketamine in normals

The clinical similarities between PCP psychosis and schizophrenia have cont ributed importantly to the development of the glutamate hypothesis of schiz ophrenia, Sensory gating, as measured by prepulse inhibition of the acousti c startle reflex (PPI), is impaired in patients with schizophrenia, In anim als, the noncompetitive NMDA antagonists PCP and ketamine disrupt PPI in a way that resembles the defect seen in schizophrenia, The purpose of this wo rk is to investigate the modulation of sensory gating in humans by subanaes thetic closes of ketamine. 16 healthy male subjects received a 60-min infus ion of ketamine (0.5 mg/kg) or normal saline on two separate days in a rand omized double-blind crossover design. Clinical ratings and PPI were none du ring the infusion on both days. Ketamine produced robust clinical effects. Dissociative symptoms as measured by the CADSS increased from 0 +/- 0.0 to 29.3 +/- 14.3; negative symptoms (Affect Rating Scale) increased from 17.2 +/- 0.8 to 24.8 +/- 3.1; and total BPRS scores increased from 18.3 +/- 0.8 to 26.4 +/- 5.1. ANOVAs for these rating were all significant at the p <.00 0 level, although BPRS increases were not in the range seen in decompensate d schizophrenic patients. The amplitudes of the startle responses to pulse- alone stimuli were not significantly different on ketamine and placebo days . Ketamine did not cause disruption in PPI as expected. On the contrary, in the first block of the PPI session ketamine significantly enhanced PPI (AN OVA; F=6.15, p =.026). These results indicate that the clinical effects of ketamine are not coupled with schizophrenic-like disruption of PPI in norma l controls. [Neuropsychopharmacology 25:72-83, 2001] (C) 2001 American Coll ege of Neuropsychopharmacology. Published by Elsevier Science Inc.