Background
This study tested the hypothesis that deficits in γ-aminobutyric acid type A (GABAA) receptor function might create a vulnerability to the psychotogenic and perceptual
altering effects of serotonergic (5-HT2A/2C) receptor stimulation. The interactive effects of iomazenil, an antagonist and partial
inverse agonist of the benzodiazepine site of the GABAA receptor complex, and m-chlorophenylpiperazine (m-CPP), a partial agonist of 5-HT2A/2C receptors, were studied in 23 healthy male subjects.
Methods
Subjects underwent 4 days of testing, during which they received intravenous infusions
of iomazenil/placebo followed by m-CPP/placebo in a double-blind, randomized crossover
design. Behavioral, cognitive, and hormonal data were collected before drug infusions
and periodically for 200 min after.
Results
Iomazenil and m-CPP interacted in a synergistic manner to produce mild psychotic symptoms
and perceptual disturbances without impairing cognition. Iomazenil and m-CPP increased
anxiety in an additive fashion. Iomazenil and m-CPP interacted in a synergistic manner
to increase serum cortisol.
Conclusions
Gamma-aminobutyric acid-ergic deficits might increase the vulnerability to the psychotomimetic
and perceptual altering effects of serotonergic agents. These data suggest that interactions
between GABAA and 5-HT systems might contribute to the pathophysiology of psychosis and dissociative-like
perceptual states.
Key Words
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Article info
Publication history
Published online: September 05, 2005
Accepted:
June 17,
2005
Received in revised form:
April 29,
2005
Received:
January 25,
2005
Identification
Copyright
© 2005 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
