Direct demonstration of the effect of lorazepam on the excitability of the human motor cortex.
OBJECTIVE
The present study explored the effects of lorazepam, a benzodiazepine with agonist action at the GABA(A) receptor, on human motor cortex excitability as tested using transcranial magnetic stimulation.


METHODS
We recorded directly the descending volley evoked by single and paired transcranial magnetic stimulation from the spinal cord of a conscious subject with a cervical epidural electrode before and after a single oral dose of lorazepam. We evaluated the effects of lorazepam on the descending volleys evoked by a single magnetic stimulation and paired cortical stimulation using the intracortical inhibition paradigm (subthreshold conditioning stimulus) and the short latency intracortical facilitation paradigm (suprathreshold conditioning stimulus).


RESULTS
Using a single magnetic stimulus lorazepam decreased the amplitude of the later I waves in the descending volley; this was accompanied by a decrease in the amplitude of the evoked EMG response. Using the intracortical inhibition paradigm lorazepam increased the amount of corticocortical inhibition, particularly at 4 and 5 ms interstimulus intervals. There was no effect on the amount of facilitation observed in the short latency intracortical facilitation paradigm.


CONCLUSIONS
The present findings provide direct evidence that lorazepam increases the excitability of inhibitory circuits in the human motor cortex.
Di Lazzaro
V
V
Istituto di Neurologia, Università Cattolica, L.go A. Gemelli 8, 00168, Rome, Italy. dilazzar@rm.ats.it
Oliviero
A
A
Meglio
M
M
Cioni
B
B
Tamburrini
G
G
Tonali
P
P
Rothwell
J C
JC
D000368:Aged; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy; D004599:Electric Stimulation Therapy; D004576:Electromyography / Q000187:drug effects; D007839:Functional Laterality; D006801:Humans; D008140:Lorazepam / Q000627:therapeutic use*; D017116:Low Back Pain / Q000503:physiopathology / Q000628:therapy; D008280:Magnetics; D009044:Motor Cortex / Q000187:drug effects* / Q000503:physiopathology; D011930:Reaction Time; D011963:Receptors, GABA-A / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000503:physiopathology
D014151:Anti-Anxiety Agents; D011963:Receptors, GABA-A; D008140:Lorazepam