A. Todorova, EFFECTS OF DIAZEPAM AND THE SPECIFIC BENZODIAZEPINE ANTAGONIST FLUMAZENIL ON SOMATOSENSORY EVOKED-POTENTIALS IN RATS, Archives internationales de pharmacodynamie et de therapie, 321, 1993, pp. 14-29
Changes in somatosensory evoked potentials were studied in 88 rats fol
lowing intravenous injections of diazepam (0.5, 1 and 5 mg/kg) and flu
mazenil (0.5 and 5 mg/kg). The antagonist effect of flumazenil against
previously administered diazepam was evaluated by somatosensory evoke
d potentials, when given in the same doses. Generally, a peak-latency
increase and an amplitude reduction were observed after diazepam admin
istration. The low dose of flumazenil led to similar changes in somato
sensory evoked potentials. The higher dose of flumazenil resulted in a
n immediate, short-lasting latency decrease of the late cortical poten
tials and an amplitude reduction with a delay in its appearance. Accor
ding to the obtained data, diazepam elicited a marked suppressive acti
on mainly on the corticocortical processing of the sensor information
with a milder effect on the thalamic level. Flumazenil showed some int
rinsic activities with the low dose effects being benzodiazepine-like
and the higher dose resulting in two overlapping opposite actions (ini
tially stimulant and subsequently suppressive). The same flumazenil do
ses, applied 30 min after injection of diazepam, were able to fully or
partially reverse (with some dose differences) the diazepam-induced l
atency prolongations, whereas flumazenil could not antagonize signific
antly the diazepam effect on the amplitudes. This may be due to the gr
eater influence of diazepam on the amplitudes.