Effects of lorazepam on short latency afferent inhibition and short latency intracortical inhibition in humans
Open Access
- 6 April 2005
- journal article
- clinical trial
- Published by Wiley in The Journal of Physiology
- Vol. 564 (2), 661-668
- https://doi.org/10.1113/jphysiol.2004.061747
Abstract
Experimental studies have demonstrated that the GABAergic system modulates acetylcholine release and, through GABAA 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 GABAA 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 GABAA 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 (F3,9= 3.19, P= 0.039). In contrast to SICI, SAI was significantly reduced by lorazepam (F3,9= 9.39, P= 0.0002). Our findings demonstrate that GABAA activity enhancement determines a suppression of SAI and an increase of SICI.Keywords
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