title: A single dose of lorazepam reduces paired-pulse suppression of median nerve evoked somatosensory evoked potentials.
abstract: Paired-pulse behaviour in the somatosensory cortex is an approach to obtain insights into cortical processing modes and to obtain markers of changes of cortical excitability attributable to learning or pathological states. Numerous studies have demonstrated suppression of the response to the stimulus that follows a first one after a short interval, but the underlying mechanisms remain elusive, although there is agreement that GABAergic mechanisms seem to play a crucial role. We therefore aimed to explore the influence of the GABAA agonist lorazepam on paired-pulse somatosensory evoked potentials (SEPs). We recorded and analysed SEPs after paired median nerve stimulation in healthy individuals before and after they had received a single dose of 2.5 mg of lorazepam as compared with a control group receiving placebo. Paired-pulse suppression was expressed as a ratio of the amplitudes of the second and the first peaks. We found that, after lorazepam application, paired-pulse suppression of the cortical N20 component remained unchanged, but suppression of the N20-P25 complex was significantly reduced, indicative of GABAergic involvement in intracortical processing. Our data suggest that lorazepam most likely enhances inhibition within the cortical network of interneurons responsible for creating paired-pulse suppression, leading to reduced inhibitory drive with a subsequently reduced amount of suppression. The results provide further evidence that GABAA -mediated mechanisms are involved in the generation of median nerve evoked paired-pulse suppression.
authors.affiliation: Department of Neurology, BG-Universitaetsklinikum Bergmannsheil Bochum, Buerkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Stude
authors.affiliation: Department of Neurology, BG-Universitaetsklinikum Bergmannsheil Bochum, Buerkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Lenz
authors.affiliation: Department of Neurology, BG-Universitaetsklinikum Bergmannsheil Bochum, Buerkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Höffken
authors.affiliation: Department of Neurology, BG-Universitaetsklinikum Bergmannsheil Bochum, Buerkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Tegenthoff
authors.affiliation: Department of Neurology, BG-Universitaetsklinikum Bergmannsheil Bochum, Buerkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.|Neural Plasticity Laboratory, Institute for Neuroinformatics, Ruhr University, Bochum, Germany.
authors.forename: Hubert
authors.initials: H
authors.lastname: Dinse
mesh_terms: D000328:Adult; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects*; D005260:Female; D058787:GABA-A Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008140:Lorazepam / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008475:Median Nerve / Q000502:physiology*; D013003:Somatosensory Cortex / Q000502:physiology
chemical_list: D058787:GABA-A Receptor Antagonists; D008140:Lorazepam
keywords: GABA; cortical excitability; intracortical inhibition; paired-pulse behaviour; plasticity; somatosensory evoked potentials