Benzodiazepine antagonist flumazenil reduces bicuculline-induced enhancement of neuronal activity in the spinal cord

Abstract

The interaction between the GABA A receptor antagonist bicuculline and the benzodiazepine receptor (BR) antagonist flumazenil was studied in the lumbosacral cord of spinal cats. Bicuculline (0.8 mg/kg i.v.) evoked epileptiform bursting of motoneurons in parallel with a depression of peripherally elicited dorsal root potentials (DRP) and dorsal root reflexes (DRR). A low dose of flumazenil (0.03 mg/kg i.v.) reduced the bursting activity of motoneurons as well as partially reversed the depression of DRP and DRR induced by bicuculline. It is suggested that an endogenous BR ligand down-regulating GABA A receptors is released during the bicuculline-evoked enhancement of neuronal activity and may contribute to the epileptiform discharge of motoneurons in the spinal cord.