| 16140281 |
D'Souza DC, Gil RB, Zuzarte E, MacDougall LM, Donahue L, Ebersole JS, Boutros NN, Cooper T, Seibyl J, Krystal JH: gamma-Aminobutyric acid-serotonin interactions in healthy men: implications for network models of psychosis and dissociation. Biol Psychiatry. 2006 Jan 15;59(2):128-37. Epub 2005 Sep 2.
BACKGROUND: This study tested the hypothesis that deficits in gamma-aminobutyric acid type A (GABA (A)) receptor function might create a vulnerability to the psychotogenic and perceptual altering effects of serotonergic (5-HT (2A/2C)) receptor stimulation. The interactive effects of iomazenil, an antagonist and partial inverse agonist of the benzodiazepine site of the GABA (A) receptor complex, and m-chlorophenylpiperazine (m-CPP), a partial agonist of 5-HT (2A/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 GABA (A) and 5-HT systems might contribute to the pathophysiology of psychosis and dissociative-like perceptual states. |
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