Effect of Vigabatrin on motor responses to transcranial magnetic stimulation: An effective tool to investigate in vivo GABAergic cortical inhibition in humans

In this study, transcranial magnetic stimulation (TMS) of the hand primary motor area was used to test possible excitability changes induced by the administration of Vigabatrin (Gamma-Vinyl-gamma-aminobutryic acid;4-amino-hex-5-enoic acid; GVG), a selective GABAergic drug, on cortical inhibitory mechanisms in healthy subjects. In a group of 15 healthy volunteers, the level of motor cortical excitability was studied by means of paired-pulse TMS (p-TMS) protocols exploring the early (1-6 ms of interstimulus intervals, ISI) and the late cortical inhibition (20-250 ms ISI), and by evaluating the cortical silent period (CSP) duration obtained in response to single pulse stimulation of cortical motor area. In all participants TMS procedures were carried out before and after administering GVG for three consecutive days at a daily dosage of 50 mg/kg. Three months later, a third TMS recording session was repeated to investigate possible long-lasting GVG effects on cortical excitability. GVG induces relevant changes of cortical excitability consisting in an increase of late cortical inhibition in response to the long ISI p-TMS and in a prolonged duration of the CSP. No significant change in the early cortical inhibition was observed in response to the short ISI p-TMS. The analysis of peripheral motor excitability was also assessed, with no effects. The present electrophysiological data show that GVG is able to induce a significant increase of the late cortical inhibition, whereas it does not affect the early cortical inhibition. These data suggest that the great availability of synaptic GABA differently acts on the inhibitory circuitries controlled by different GABA-receptor subtypes.