Journal
NEUROPHARMACOLOGY
Volume 88, Issue -, Pages 155-163Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2014.08.017
Keywords
GABA; Magnetoencephalography; Human; Zolpidem; Gaboxadol; Tiagabine
Categories
Funding
- Psychopharmacology Unit, Dept Academic Psychiatry, University of Bristol
- CUBRIC, Dept Psychology, Cardiff University
- Medical Research Council [G1002226, G0400575] Funding Source: researchfish
- MRC [G0400575, G1002226] Funding Source: UKRI
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A range of medications target different aspects of the GABA system; understanding their effects is important to inform further drug development. Effects on the waking EEG comparing these mechanisms have not been reported; in this study we compare the effects on resting MEG spectra of the benzodiazepine receptor agonist zolpidem, the delta sub-unit selective agonist gaboxadol (also known as THIP) and the GABA reuptake inhibitor tiagabine. These were two randomised, single-blind, placebo-controlled, crossover studies in healthy volunteers, one using zolpidem 10 mg, gaboxadol 15 mg and placebo, and the other tiagabine 15 mg and placebo. Whole head MEG recordings and individual MEG spectra were divided into frequency bands. Baseline spectra were subtracted from each post-intervention spectra and then differences between intervention and placebo compared. After zolpidem there were significant increases in beta frequencies and reduction in alpha frequency power; after gaboxadol and tiagabine there were significant increases in power at all frequencies up to beta. Enhancement of tonic inhibition via extrasynaptic receptors by gaboxadol gives rise to a very different MEG signature from the synaptic action of zolpidem. Tiagabine theoretically can affect both types of receptor; from these MEG results it is likely that the latter is the more prominent effect here. (C) 2014 The Authors. Published by Elsevier Ltd.
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