Low dose ketamine increases prepulse inhibition in healthy men

The N-methyl-D-aspartate (NMDA) antagonist, ketamine, produces neurobehavioural symptoms that mimic aspects of schizophrenia. Prepulse inhibition (PPI) of the startle reflex, a measure of sensorimotor gating, is decreased in chronically ill, medicated schizophrenic patients and in animals treated acutely with NMDA antagonists. We tested the hypothesis that ketamine would produce psychotic symptoms and reduce PPI in healthy humans. Twenty male volunteers received placebo and ketamine in a within-subject, double-blind, cross-over design with 0.23 mg/kg ketamine hydrochloride or saline as a loading dose, followed by 0.5 mg/kg ketamine or saline over 45 min. Prepulse to pulse intervals were 30 ms and 120 ms. The Brief Psychiatric Rating Scale (BPRS) and the Clinician Administered Dissociative States Scale (CADSS) were administered. Ketamine produced a significant increase in PPI and significantly reduced startle magnitude, but did not alter habituation. Ketamine produced significant increases in BPRS and CADSS scores, with symptoms mimicking the negative and disorganisation symptoms of psychosis. In contrast to effects in rodents, this low dose of ketamine produced an increase in PPI despite producing psychopathological symptoms consistent with the NMDA psychosis model. These findings suggest that the cognitive and PPI changes of NMDA antagonists are not consistently linked at a phenomenological or neurochemical level.