Clinical and Sensorimotor Gating Effects of Ketamine in Normals

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 25; no. 1; pp. 72 - 83
• Main Authors: Duncan, Erica J., Madonick, Steven H., Parwani, Arti, Angrist, Burt, Rajan, Rajive, Chakravorty, Subhajit, Efferen, Toby R., Szilagyi, Sandor, Stephanides, Myrsini, Chappell, Phillip B., Gonzenbach, Stephen, Ko, Grant N., Rotrosen, John P.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.07.2001; Nature Publishing; Nature Publishing Group
• Subjects: Acoustic startle; Adult; Adult and adolescent clinical studies; Affect - drug effects; Affect - physiology; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Brain - physiopathology; Cardiovascular Physiological Phenomena - drug effects; Excitatory Amino Acid Antagonists - administration & dosage; Excitatory Amino Acid Antagonists - adverse effects; Glutamic Acid - metabolism; Habituation; Hallucinations - chemically induced; Hallucinations - physiopathology; Humans; Ketamine; Ketamine - administration & dosage; Ketamine - adverse effects; Male; Medical sciences; Neural Inhibition - drug effects; Neural Inhibition - physiology; Neurons - drug effects; Neurons - metabolism; Neuropsychological Tests; Prepulse inhibition; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Reaction Time - drug effects; Reaction Time - physiology; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - metabolism; Reference Values; Reflex, Startle - drug effects; Reflex, Startle - physiology; Schizophrenia; Sensorimotor gating; Sensorimotor gating; Schizophrenia; Ketamine; Acoustic startle; Prepulse inhibition; Habituation; Human; Intravenous administration; Healthy subject; Toxicity; Startle reflex; Psychosis; Acoustic stimulus; Investigation method; Negative symptom; Clinical trial; Models; Hemodynamics; Inhibition; Blinking; Positive symptom
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1016/S0893-133X(00)00240-2

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.