S-ketamine and GABA-A-receptor interaction in humans: an exploratory study with I-123-iomazenil SPECT

• Published in: Human psychopharmacology Vol. 23; no. 7; pp. 549 - 554
• Main Authors: Heinzel, Alexander, Steinke, Rainer, Poeppel, Thorsten Dirk, Grosser, Oliver, Bogerts, Bernhard, Otto, Hans, Northoff, Georg
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.10.2008
• Subjects: Adult; Analysis of Variance; Anesthetics, Dissociative - blood; Anesthetics, Dissociative - pharmacology; Brain Mapping; Brief Psychiatric Rating Scale; Case-Control Studies; Cerebral Cortex - diagnostic imaging; Cerebral Cortex - drug effects; Female; Flumazenil - analogs & derivatives; GABA-A; Humans; Hydrocortisone - blood; I-123-iomazenil; Iodine Radioisotopes; Ketamine - blood; Ketamine - pharmacology; Male; medial prefrontal cortex; Prolactin - blood; Receptors, GABA-A - physiology; S-ketamine; SPECT; Tomography, Emission-Computed, Single-Photon; Young Adult
• ISSN: 0885-6222; 1099-1077; 1099-1077
• DOI: 10.1002/hup.960

Objective We aimed to probe for regional cerebral effects of S‐ketamine on in vivo GABA‐A‐receptor binding in healthy human subjects. Methods We investigated I‐123‐iomazenil SPECT before, during and after administration of S‐ketamine in a blinded placebo‐controlled study design (n = 12 in both groups). Analyses of SPECT were performed with voxel‐based statistical parametric mapping (SPM), and statistical comparisons were made between the groups. We also assessed biochemical and behavioural changes during S‐ketamine infusion. Results S‐ketamine induced positive and negative symptoms measured by the Brief Psychiatric Rating scale (BPRS). It increased the cortisol and prolactin levels. Image analysis revealed significantly decreased I‐123‐iomazenil binding in bilateral dorsomedial prefrontal cortex during S‐ketamine administration when compared to placebo. Conclusion Our study delivers preliminary evidence for an in vivo interaction of S‐ketamine with GABA‐A‐receptors in human dorsomedial prefrontal cortex. Copyright © 2008 John Wiley & Sons, Ltd.