The ability of various drugs to prevent the onset of
status epilepticus induced by administration of the
muscarinic agonist,
pilocarpine, to
lithium-pretreated rats was determined. Motor limbic
seizures and
status epilepticus occurred in 100% of rats administered
pilocarpine (30 mg/kg, s.c.) 20 h after pretreatment with
lithium (3 meq/kg, i.p.). The latency to spike activity and to
status epilepticus was 20 +/- 1 min and 24 +/- 1 min, respectively.
Atropine,
diazepam,
phenytoin,
carbamazepine,
phenobarbital,
paraldehyde, and
L-phenylisopropyladenosine (L-PIA) prevented all phases of seizure activity induced by
lithium/
pilocarpine treatment. The initiation of
status epilepticus was significantly prolonged by pretreatment with
sodium valproate. These findings indicate that the
seizures induced by administration of
lithium and
pilocarpine accurately model generalized
tonic-clonic epilepsy. The
anticonvulsant activity of L-PIA was prevented by prior treatment with the
adenosine antagonist,
theophylline. The latency to spike and seizure activity was decreased by
theophylline, indicating that endogenous
adenosine may have a tonic inhibitory influence on cholinergic neurons.
Atropine,
diazepam,
phenobarbital,
phenytoin, sodium valproate, L-PIA, and
carbamazepine did not interrupt seizure activity when administered 60 min after
pilocarpine (approximately 35 min after initiation of
status epilepticus). When rats were administered
paraldehyde at this time,
status epilepticus was rapidly terminated and all rats survived. Thus,
status epilepticus induced by
lithium and
pilocarpine provides a seizure model that is not responsive to conventional
anticonvulsants.