Di Lazzaro V, Pilato F, Dileone M, Profice P, Ranieri F, Ricci V, Bria P, Tonali P A, Ziemann U
Institute of Neurology, Università Cattolica, L go A Gemelli 8, 00168 Rome, Italy.
Clin Neurophysiol. 2007 Oct;118(10):2207-14. doi: 10.1016/j.clinph.2007.07.005. Epub 2007 Aug 20.
To investigate if different interneuronal circuits in human motor cortex mediate inhibition through different subtypes of the gamma-aminobutyric acid A receptor (GABAAR).
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 (SAI). 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 alpha1- than alpha2- or alpha3-subunit bearing GABAARs, no affinity to alpha5-subunits) was tested in a randomized crossover design. In addition, the sedative drug effects were recorded by a visual analogue scale.
Diazepam and lorazepam increased SICI, whereas zolpidem did not change SICI. In contrast, diazepam had no effect on SAI, whereas lorazepam and zolpidem decreased SAI. The sedative effects were not different between drugs.
The dissociating patterns of drug modification of SICI versus SAI strongly suggest that different GABAAR subtypes are involved in SICI and SAI.
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 benzodiazepines on SAI and SICI suggest that neuronal circuits in human motor cortex that mediate inhibition through different GABAAR subtypes can be segregated by TMS.
研究人类运动皮层中不同的中间神经元回路是否通过不同亚型的γ-氨基丁酸A受体（GABAAR）介导抑制作用。
采用既定的经颅磁刺激（TMS）方案，在10名健康受试者中测量两种不同形式的运动皮层抑制：短间隔皮层内抑制（SICI）和短潜伏期传入抑制（SAI）。通过随机交叉设计，测试单次口服三种不同的GABAAR阳性调节剂（20毫克地西泮、2.5毫克劳拉西泮和10毫克唑吡坦）对它们的影响，这三种调节剂对GABAAR不同α亚基亚型具有不同的亲和力（地西泮：非选择性；劳拉西泮：未知；唑吡坦：对含α1亚基的GABAAR的亲和力比对含α2或α3亚基的GABAAR高10倍，对α5亚基无亲和力）。此外，通过视觉模拟量表记录镇静药物效果。
地西泮和劳拉西泮增加SICI，而唑吡坦不改变SICI。相反，地西泮对SAI无影响，而劳拉西泮和唑吡坦降低SAI。药物之间的镇静效果无差异。
SICI与SAI的药物修饰解离模式强烈表明，不同的GABAAR亚型参与了SICI和SAI。
我们首次提供了地西泮和唑吡坦对SAI作用解离的证据，并证实了先前报道的唑吡坦以及地西泮和劳拉西泮对SICI的不同作用。三种苯二氮䓬类药物对SAI和SICI的不同作用表明，人类运动皮层中通过不同GABAAR亚型介导抑制的神经元回路可通过TMS进行区分。
