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Dissociated effects of diazepam and lorazepam on short‐latency afferent inhibition
Author(s) -
Di Lazzaro Vincenzo,
Pilato Fabio,
Dileone Michele,
Tonali Pietro A.,
Ziemann Ulf
Publication year - 2005
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2005.092155
Subject(s) - lorazepam , transcranial magnetic stimulation , diazepam , benzodiazepine , gabaa receptor , neuroscience , cholinergic , stimulation , motor cortex , inhibitory postsynaptic potential , psychology , chemistry , pharmacology , receptor , anesthesia , medicine
Peripheral nerve inputs have an inhibitory effect on motor cortex excitability at short intervals (short‐latency afferent inhibition, SAI). This can be tested by coupling electrical stimulation of peripheral nerve with transcranial magnetic stimulation (TMS) of the motor cortex. SAI is reduced by the anticholinergic drug scopolamine, and in patients with Alzheimer's disease. Therefore, it is possible that SAI is a marker of central cholinergic activity important for memory function. The benzodiazepine lorazepam also reduces SAI. Since benzodiazepines impair memory formation, but do not do so uniformly, with a maximum amnesic effect after lorazepam but less or no effect after diazepam, we were interested in testing in this non‐behavioural study to what extent the effects of lorazepam and diazepam on circuits involved in SAI could be dissociated. In addition, and for control, we tested the effects of lorazepam and diazepam on short‐interval intracortical inhibition (SICI), a motor cortical inhibition mediated through the GABA A receptor. Lorazepam markedly reduced SAI, whereas diazepam slightly increased it. In contrast, both benzodiazepines uniformly increased SICI. Our findings demonstrate opposite effects of lorazepam and diazepam on SAI, an inhibition modulated by central cholinergic activity, but the same effects on SICI, a marker of neurotransmission through the GABA A receptor. This dissociation suggests, for the first time, that TMS measures of cortical inhibition provide the opportunity to segregate differences of benzodiazepine action in human central nervous system circuits.