γ-Aminobutyric Acid–Serotonin Interactions in Healthy Men: Implications for Network Models of Psychosis and Dissociation

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• 作者：Deepak Cyril D’ ; Souza ; Roberto B. Gil ; Edward Zuzarte ; Lisa M. MacDougall ; Lia Donahue ; John S. Ebersole ; Nashaat N. Boutros ; Tom Cooper ; John Seibyl and John H. Krystal
• 刊名：Biological Psychiatry
• 出版年：2006
• 出版时间：15 January 2006
• 年：2006
• 卷：59
• 期：2
• 页码：128-137
• 全文大小：394 K

文摘

Background

This study tested the hypothesis that deficits in γ-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.