Benzodiazepine antagonist flumazenil reduces bicuculline-induced enhancement of neuronal activity in the spinal cord.
The interaction between the GABAA 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 (DDR). 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 GABAA receptors is released during the bicuculline-evoked enhancement of neuronal activity and may contribute to the epileptiform discharge of motoneurons in the spinal cord.
Polc
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Pharma Research Department, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Ducić
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D000818:Animals; D001640:Bicuculline / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002415:Cats; D004827:Epilepsy / Q000503:physiopathology; D005071:Evoked Potentials / Q000187:drug effects; D005442:Flumazenil / Q000494:pharmacology*; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology
D011963:Receptors, GABA-A; D005442:Flumazenil; D001640:Bicuculline