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This Article Full Text Full Text (PDF) All Versions of this Article: 575/3/721    most recent jphysiol.2006.114694v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Di Lazzaro, V. Articles by Ziemann, U. Search for Related Content PubMed PubMed Citation Articles by Di Lazzaro, V. Articles by Ziemann, U. Related Collections Neuroscience

¹ Institutes of Neurology
² Psychiatry, Università Cattolica, L.go A. Gemelli 8, 00168 Rome, Italy
³ Fondazione Don C Gnocchi, Rome, Italy
⁴ Department of Neurology, Johann Wolfgang Goethe-University, Frankfurt, Germany

Inhibition is of fundamental importance to regulate activity in cortical circuits. Inhibition is mediated through a diversity of different interneurones and -aminobutyric acid A receptor (GABA_AR) subtypes. Here we employed paired-pulse transcranial magnetic stimulation (TMS) to measure short interval intracortical inhibition (SICI), a GABA_AR-mediated inhibition in human motor cortex, to address the question of which GABA_AR subtype is responsible for this form of inhibition. It has been shown that classical benzodiazepines (diazepam and lorazepam) have a non-selective affinity profile at different -subunit-bearing subtypes of the GABA_AR while zolpidem has a 10-fold greater affinity to the 1-subunit-bearing GABA_AR compared with those bearing the 2- or 3-subunit. We found that, in seven healthy subjects, a single oral dose of 20 mg of diazepam or 2.5 mg of lorazepam significantly increased SICI, whereas 10 mg of zolpidem did not change SICI. This dissociation occurred despite equal sedation by all three drugs, an 1-subunit GABA_AR-mediated effect. The findings strongly suggest that SICI is not mediated by the 1-subunit-bearing subtype of the GABA_AR but by those bearing either the 2- or 3-subunit. This study represents an attempt by means of TMS to identify GABA_AR subtype-specific action at the systems level of human cortex, a highly relevant issue because the different -subunit-bearing subtypes of the GABA_AR are differently involved in benzodiazepine-mediated effects such as sedation, amnesia or anxiolysis, in developmental cortical plasticity, and in neurological disorders such as epilepsy.

(Received 3 June 2006; accepted after revision 27 June 2006; first published online 29 June 2006)
Corresponding author V. Di Lazzaro: Istituto di Neurologia, Università Cattolica, L.go A. Gemelli 8, 00168 Rome, Italy. Email: vdilazzaro{at}rm.unicatt.it U. Ziemann: Department of Neurology, JW Goethe-University of Frankfurt, Germany. Email: u.ziemann{at}em.uni-frankfurt.de

This article has been cited by other articles:

				J. Florian, M. Muller-Dahlhaus, Y. Liu, and U. Ziemann Inhibitory circuits and the nature of their interactions in the human motor cortex a pharmacological TMS study J. Physiol., January 15, 2008; 586(2): 495 - 514. [Abstract] [Full Text] [PDF]