Clinical and sensorimotor gating effects of ketamine in normals.
E J Duncan, S H Madonick, A Parwani, B Angrist, R Rajan, S Chakravorty, T R Efferen, S Szilagyi, M Stephanides, P B Chappell, S Gonzenbach, G N Ko, J P Rotrosen
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology July 1, 2001 DOI: 10.1016/s0893-133x(00)00240-2 via PubMed
Summary
AI-generated from the abstractKetamine, a drug that blocks NMDA receptors, produces schizophrenia-like symptoms in healthy people but does not disrupt sensory gating in the same way schizophrenia does. In a randomized double-blind crossover study, 16 healthy men received a 60-minute infusion of either ketamine (0.5 mg/kg) or saline. Ketamine caused robust dissociative and negative symptoms, but it did not impair prepulse inhibition (PPI) of the startle reflex; instead, it significantly enhanced PPI in the first block. These results indicate that ketamine's clinical effects are not coupled with the PPI disruption seen in schizophrenia.
Study at a glance
| Characteristics | Randomized double-blind crossover design Peer reviewed |
|---|---|
| Sample size | 16 |
| Population | Healthy male subjects |
| Interventions | Ketamine normal saline |
| Dose | 0.5 mg/kg |
| Duration | 60-minute infusion |
| Key finding | Ketamine enhanced prepulse inhibition rather than disrupting it, indicating its clinical effects are not coupled with schizophrenic-like PPI disruption. |
Abstract
The clinical similarities between PCP psychosis and schizophrenia have contributed importantly to the development of the glutamate hypothesis of schizophrenia. Sensory gating, as measured by prepulse inhibition of the acoustic startle reflex (PPI), is impaired in patients with schizophrenia. In animals, the noncompetitive NMDA antagonists PCP and ketamine disrupt PPI in a way that resembles the defect seen in schizophrenia. The purpose of this work is to investigate the modulation of sensory gating in humans by subanaesthetic doses of ketamine. 16 healthy male subjects received a 60-min infusion of ketamine (0.5 mg/kg) or normal saline on two separate days in a randomized double-blind crossover design. Clinical ratings and PPI were done during 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 ratings were all significant at the p <.000 level, although BPRS increases were not in the range seen in decompensated 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 (ANOVA; F=6.15, p =.026). These results indicate that the clinical effects of ketamine are not coupled with schizophrenic-like disruption of PPI in normal controls.