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Low dose ketamine increases prepulse inhibition in healthy men
Kathryn M Abel1, Matthew P G Allin, David R Hemsley
17th Floor Williamson Building, University of Manchester, Manchester M13 9PL, UK. k.abel@iop.kcl.ac.uk
Neuropharmacology
|April 12, 2003
Summary
Ketamine, an N-methyl-D-aspartate (NMDA) antagonist, induced psychosis-like symptoms in healthy humans but unexpectedly increased prepulse inhibition (PPI), a measure of sensorimotor gating. This challenges the direct link between NMDA antagonist-induced psychosis and sensorimotor gating deficits.
Area of Science:
- Neuroscience
- Psychiatry
- Pharmacology
Background:
- N-methyl-D-aspartate (NMDA) antagonists like ketamine can induce psychosis-like symptoms.
- Prepulse inhibition (PPI) of the startle reflex is a measure of sensorimotor gating, often reduced in schizophrenia and by NMDA antagonists in animals.
- Previous research suggests a link between NMDA antagonist effects, psychosis, and reduced PPI.
Purpose of the Study:
- To investigate whether ketamine administration in healthy humans produces psychotic symptoms and affects PPI.
- To test the hypothesis that ketamine would reduce PPI in humans, consistent with animal models and schizophrenia.
Main Methods:
- A within-subject, double-blind, cross-over design was used with 20 male volunteers.
- Participants received placebo or ketamine (loading dose followed by infusion).
- Psychotic symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS) and Clinician Administered Dissociative States Scale (CADSS); PPI was measured at 30 ms and 120 ms intervals.
Main Results:
- Ketamine significantly increased BPRS and CADSS scores, mimicking negative and disorganized symptoms of psychosis.
- Contrary to expectations, ketamine significantly increased PPI and reduced startle magnitude.
- No alteration in habituation was observed.
Conclusions:
- Low-dose ketamine in humans produces psychopathological symptoms consistent with the NMDA receptor hypofunction model of psychosis.
- The findings indicate that ketamine increased PPI, contradicting the hypothesis and previous animal findings.
- The cognitive and PPI effects of NMDA antagonists may not be consistently linked at phenomenological or neurochemical levels.