Effects of diazepam and the specific benzodiazepine antagonist flumazenil on somatosensory evoked potentials in rats.
Changes in somatosensory evoked potentials were studied in 88 rats following intravenous injections of diazepam (0.5, 1 and 5 mg/kg) and flumazenil (0.5 and 5 mg/kg). The antagonist effect of flumazenil against previously administered diazepam was evaluated by somatosensory evoked potentials, when given in the same doses. Generally, a peak-latency increase and an amplitude reduction were observed after diazepam administration. The low dose of flumazenil led to similar changes in somatosensory evoked potentials. The higher dose of flumazenil resulted in an immediate, short-lasting latency decrease of the late cortical potentials and an amplitude reduction with a delay in its appearance. According to the obtained data, diazepam elicited a marked suppressive action mainly on the corticocortical processing of the sensor information with a milder effect on the thalamic level. Flumazenil showed some intrinsic activities with the low dose effects being benzodiazepine-like and the higher dose resulting in two overlapping opposite actions (initially stimulant and subsequently suppressive). The same flumazenil doses, applied 30 min after injection of diazepam, were able to fully or partially reverse (with some dose differences) the diazepam-induced latency prolongations, whereas flumazenil could not antagonize significantly the diazepam effect on the amplitudes. This may be due to the greater influence of diazepam on the amplitudes.
Todorova
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Department of Pharmacology and Toxicology, Faculty of Pharmacy, Higher Medical Institute, Sofia, Bulgaria.
D000818:Animals; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects*; D005442:Flumazenil / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D005442:Flumazenil; D003975:Diazepam