Repeated administration of subconvulsant doses of GABA antagonist drugs. I. Effect on seizure threshold (kindling)

Repeated subconvulsant doses of the GABA antagonist drugs picrotoxin (5 mg/kg), pentylenetetrazol (PTZ) (30 mg/kg), and bicuculline (3.5 mg/kg), were given IP once daily to rats. Picrotoxin produced rapid kindling to full seizures in about 5 days, PTZ produced sporadic myoclonic seizures after 17 days, PTZ produced sporadic myoclonic seizures after 17 days whereas bicuculline only produced occasional mild jerking. Following these treatments, seizure thresholds to these drugs were measured by an IV infusion method to minimise problems of systemic uptake and metabolism of the drugs. Picrotoxin- and PTZ-treated animals showed no alteration in seizure threshold. However, following bicuculline pretreatment, seizure threshold was raised. Methodological problems in the interpretation of pharmacological kindling are discussed.