Inhibition in the somatosensory system: An integrative neuropharmacological and neuroimaging approach.

ABSTRACT

The presented study investigates the functional role of GABA in somatosensory processing, using a combined neuropharmacological-neuroimaging approach. Three different GABA agonists (GABAA alprazolam, ethanol; GABAB baclofen) were investigated in a double blind cross-over design in 16 male participants, accomplishing a tactile perception task. Somatosensory evoked magnetic fields modulated by GABAR-agonists and placebo were recorded using whole-head magnetoencephalography. Peak latencies and amplitudes of primary (SI) and secondary (SII) somatosensory cortex source activities confirmed the previously reported role of GABA as a modulator of somatosensory processing. Significant inhibitory effects on the latency of SII and on the amplitude of SI and SII were found exclusively for alprazolam, a positive allosteric modulator at GABAA receptors. The GABAB agonist baclofen did not have any modulatory effect. Moreover, we investigated whether the observed effects of alprazolam on the level of SII were explainable by the mere propagation of activity from SI to SII modulated by GABAA receptors, independently from any further GABAA-mediated inhibition in SII. By estimating the transfer function between SI and SII activation under placebo conditions, we were able to predict SII activity for the administration of GABA receptors agonists under the assumption that GABA exclusively acts at the level of SI. By comparing measured and predicted data, we propose a model in which the initial activation of SI is modulated through GABAA receptors and subsequently propagated to SII, without any significant further inhibition. In addition, initial GABAA effects in SI appear to be strongly potentiated with time, selectively in SI but not in SII.