Τίτλος:
Lorazepam-induced effects on silent period and corticomotor excitability
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
TMS studies on the CNS effects of benzodiazepines have provided
contradictory results. The objective of this study is to describe the
effects of lorazepam on silent period (SP) and corticomotor
excitability. Twelve healthy male subjects (median age 35 years) were
studied at baseline, following i.v. lorazepam administration and after
reversal of the benzodiazepine effects with i.v. flumazenil. Lorazepam
was given at a low-dose in one subject (0.0225 mg/kg bolus + 2 mu g/kg/h
infusion) and at a high-dose (0.045 mg/kg bolus + 2.6 mu g/kg/h
infusion) in the rest. Threshold (Thr) was measured at 1% steps. SPs
were investigated with two complementary methods. First, SPs were
elicited using a wide range of stimulus intensities (SIs) (from 5 to
100% maximum SI at 5% increments). At each SI, four SPs were obtained
and the average value of SP duration was used to construct a
stimulus/response (S/R) curve of SI versus SP .The resulting S/R curves
were then fitted to a Boltzman function, the best-fit values of which
were statistically compared for each experimental condition (i.e.,
baseline vs. lorazepam vs. flumazenil). Second, a large number of SPs
(n=100) was elicited during each of the three experimental conditions
using blocks of four stimuli with an intensity alternating between MT
and 200% MT. This method was employed so as to reveal the dynamic,
time-varying effects of lorazepam and flumazenil on SP duration at two
stimulus intensity (SI) levels. MEP recruitment curves were constructed
at rest and during activation and fitted to a Boltzman function the
best-fit values of which were statistically compared for each
experimental condition. Lorazepam at a low dose did not affect Thr, SP,
or the active MEP recruitment curves. The high dose also had no effect
on Thr and the active MEPs whereas the resting MEP recruitment curves
were depressed post-lorazepam at the higher range of stimulus
intensities. With regard to SP, the Max value of the S/R curve decreased
from 251 +/- 4.6 ms at baseline to 215.2 +/- 3.1 ms post-lorazepam (P <
0.01). V50 also decreased significantly (from 47.92 +/- 0.9% to 43.73
+/- 0.81%, P < 0.01) whereas there was no significant change regarding
slope and SP Thr. The statistical analysis of the SP S/R curves as well
as the study of SPs at two SI levels revealed that lorazepam reduced SP
duration when high intensity stimuli were used (> 60%). In contrast, at
low SIs a small increase in SP duration was noted post-drug. Enhancement
of GABAergic inhibition by lorazepam results in a reduction of SP
duration when high SIs is used. At the lower range of SIs, a small but
statistically significant increase in SP duration is observed. The
kinetic behavior of this phenomenon as well as the possible underlying
mechanisms are discussed.
Συγγραφείς:
Kimiskidis, V. K.
Papagiannopoulos, S.
Kazis, D. A. and
Sotirakoglou, K.
Vasiliadis, G.
Zara, F.
Kazis, A. and
Mills, K. R.
Περιοδικό:
Experimental Brain Research
Λέξεις-κλειδιά:
lorazepam; transcranial magnetic stimulation; silent period
DOI:
10.1007/s00221-006-0402-1
