Segregating two inhibitory circuits in human motor cortex at the level of GABAA receptor subtypes: A TMS study

被引:183
作者
Di Lazzaro, V. [1 ]
Pilato, F.
Dileone, M.
Profice, P.
Ranieri, F.
Ricci, V.
Bria, P.
Tonali, P. A.
Ziernann, U.
机构
[1] Univ Frankfurt, Dept Neurol, Frankfurt, Germany
[2] Univ Cattolica L go A Gemelli, Neurol Inst, I-00168 Rome, Italy
[3] Univ Cattolica L go A Gemelli, Inst Psychiat, I-00168 Rome, Italy
[4] Fdn Don C Gnocchi, Rome, Italy
关键词
short interval intracortical inhibition; short latency afferent inhibition; benzodiazepines; transcranial magnetic stimulation;
D O I
10.1016/j.clinph.2007.07.005
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objective: To investigate if different interneuronal circuits in human motor cortex mediate inhibition through different subtypes of the gamma-aminobutyric acid A receptor (GABAAR). Methods: Two distinct forms of motor cortical inhibition were measured in 10 healthy subjects by established transcranial magnetic stimulation (TMS) protocols: short interval intracortical inhibition (SICI) and short latency afferent inhibition (SA I). Their modification by a single oral dose of three different positive GABAAR modulators (20 mg of diazepam, 2.5 mg of lorazepam and 10 mg of zolpidem) with different affinity profiles at the various alpha-subunit bearing subtypes of the GABAAR (diazepam: non-selective, lorazepam: unknown, zolpidem: 10-fold higher affinity to alpha 1- than alpha 2- or alpha 3-subunit bearing GABAARs, no affinity to alpha 5-subunits) was tested in a randomized crossover design. In addition, the sedative drug effects were recorded by a visual analogue scale. Results: Diazepam and lorazepam increased SICI, whereas zolpidem did not change SICI. In contrast, diazepam had no effect on SAL whereas lorazepam and zolpidem decreased SAL The sedative effects were not different between drugs. Conclusions: The dissociating patterns of drug modification of SICI versus SAI strongly suggest that different GABAAR subtypes are involved in SICI and SAI. Significance: We provide evidence, for the first time, for a dissociation of effects of diazepam and zolpidem on SAI and confirm the previously reported differential effect of zolpidem and of diazepam and lorazepam on SICI. The differential effects of the three benzodiaze-pines on SAI and SICI suggest that neuronal circuits in human motor cortex that mediate inhibition through different GABAAR subtypes can be segregated by TMS. (C) 2007 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:2207 / 2214
页数:8
相关论文
共 55 条
[1]  
Bacci A, 2003, J NEUROSCI, V23, P9664
[2]  
CHERNIK DA, 1990, J CLIN PSYCHOPHARM, V10, P244
[3]  
CURRAN HV, 1991, PSYCHOPHARMACOLOGY, V103, P83
[4]  
Di Lazzaro V, 1998, EXP BRAIN RES, V119, P265
[5]   The physiological basis of transcranial motor cortex stimulation in conscious humans [J].
Di Lazzaro, V ;
Oliviero, A ;
Pilato, F ;
Saturno, E ;
Dileone, M ;
Mazzone, P ;
Insola, A ;
Tonali, PA ;
Rothwell, JC .
CLINICAL NEUROPHYSIOLOGY, 2004, 115 (02) :255-266
[6]   Dissociated effects of diazepam and lorazepam on short-latency afferent inhibition [J].
Di Lazzaro, V ;
Pilato, F ;
Dileone, M ;
Tonali, PA ;
Ziemann, U .
JOURNAL OF PHYSIOLOGY-LONDON, 2005, 569 (01) :315-323
[7]   Neurophysiological predictors of long term response to AChE inhibitors in AD patients [J].
Di Lazzaro, V ;
Oliviero, A ;
Pilato, F ;
Saturno, E ;
Dileone, M ;
Marra, C ;
Ghirlanda, S ;
Ranieri, F ;
Gainotti, G ;
Tonali, P .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 2005, 76 (08) :1064-1069
[8]   Direct demonstration of the effect of lorazepam on the excitability of the human motor cortex [J].
Di Lazzaro, V ;
Oliviero, A ;
Meglio, M ;
Cioni, B ;
Tamburrini, G ;
Tonali, P ;
Rothwell, JC .
CLINICAL NEUROPHYSIOLOGY, 2000, 111 (05) :794-799
[9]   Effects of lorazepam on short latency afferent inhibition and short latency intracortical inhibition in humans [J].
Di Lazzaro, V ;
Oliviero, A ;
Saturno, E ;
Dileone, M ;
Pilato, F ;
Nardone, R ;
Ranieri, F ;
Musumeci, G ;
Fiorilla, T ;
Tonali, P .
JOURNAL OF PHYSIOLOGY-LONDON, 2005, 564 (02) :661-668
[10]   Motor cortex hyperexcitability to transcranial magnetic stimulation in Alzheimer's disease [J].
Di Lazzaro, V ;
Oliviero, A ;
Pilato, F ;
Saturno, E ;
Dileone, M ;
Marra, C ;
Daniele, A ;
Ghirlanda, S ;
Gainotti, G ;
Tonali, PA .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 2004, 75 (04) :555-559