Effects of lorazepam on short latency afferent inhibition and short latency intracortical inhibition in humans

J Physiol. 2005 Apr 15;564(Pt 2):661-8. doi: 10.1113/jphysiol.2004.061747. Epub 2005 Feb 17.


Experimental studies have demonstrated that the GABAergic system modulates acetylcholine release and, through GABA(A) receptors, tonically inhibits cholinergic activity. Little is known about the effects of GABA on the cholinergic activity in the human central nervous system. In vivo evaluation of some cholinergic circuits of the human brain has recently been introduced using a transcranial magnetic stimulation (TMS) protocol based on coupling peripheral nerve stimulation with TMS of the motor cortex. Peripheral nerve inputs have an inhibitory effect on motor cortex excitability at short intervals (short latency afferent inhibition, SAI). We investigated whether GABA(A) activity enhancement by lorazepam modifies SAI. We also evaluated the effects produced by lorazepam on a different TMS protocol of cortical inhibition, the short interval intracortical inhibition (SICI), which is believed to be directly related to GABA(A) activity. In 10 healthy volunteers, the effects of lorazepam were compared with those produced by quetiapine, a psychotropic drug with sedative effects with no appreciable affinity at cholinergic muscarinic and benzodiazepine receptors, and with those of a placebo using a randomized double-blind study design. Administration of lorazepam produced a significant increase in SICI (F(3,9) = 3.19, P = 0.039). In contrast to SICI, SAI was significantly reduced by lorazepam (F(3,9) = 9.39, P = 0.0002). Our findings demonstrate that GABA(A) activity enhancement determines a suppression of SAI and an increase of SICI.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Analysis of Variance
  • Double-Blind Method
  • Electromagnetic Fields
  • Evoked Potentials, Motor / drug effects
  • Evoked Potentials, Motor / physiology
  • Humans
  • Lorazepam / pharmacology*
  • Motor Cortex / drug effects*
  • Motor Cortex / physiology
  • Neural Inhibition / drug effects*
  • Neural Inhibition / physiology
  • Neurons, Afferent / drug effects*
  • Neurons, Afferent / physiology
  • Reaction Time / drug effects*
  • Reaction Time / physiology
  • Time Factors


  • Lorazepam