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

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.