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.


CONCLUSIONS
Our study delivers preliminary evidence for an in vivo interaction of S-ketamine with GABA-A-receptors in human dorsomedial prefrontal cortex.
Department of Psychiatry, University of Magdeburg, Magdeburg, Germany. a.heinzel@fz-juelich.de
Alexander
A
Heinzel
Rainer
R
Steinke
Thorsten Dirk
TD
Poeppel
Oliver
O
Grosser
Bernhard
B
Bogerts
Hans
H
Otto
Georg
G
Northoff
D000328:Adult; D000704:Analysis of Variance; D000778:Anesthetics, Dissociative / Q000097:blood / Q000494:pharmacology*; D001931:Brain Mapping; D010054:Brief Psychiatric Rating Scale; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000187:drug effects*; D005260:Female; D005442:Flumazenil / Q000031:analogs & derivatives; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007457:Iodine Radioisotopes; D007649:Ketamine / Q000097:blood / Q000494:pharmacology*; D008297:Male; D011388:Prolactin / Q000097:blood; D011963:Receptors, GABA-A / Q000502:physiology*; D015899:Tomography, Emission-Computed, Single-Photon; D055815:Young Adult
D000778:Anesthetics, Dissociative; D007457:Iodine Radioisotopes; D011963:Receptors, GABA-A; D005442:Flumazenil; D007649:Ketamine; C063038:iomazenil; D011388:Prolactin; D006854:Hydrocortisone