Status epilepticus is produced by administration of cholinergic agonists to lithium-treated rats: comparison with kainic acid

Abstract

Electroencephalographic techniques were used to study generalized convulsive status epilepticus induced by administration of subconvulsive doses of cholinomimetics (e.g., pilocarpine) to rats pretreated with lithium chloride. Status epilepticus induced by this treatment was compared with status epilepticus induced by kainic acid. Lithium/pilocarpine-induced status epilepticus developed within 10 min of initial paroxysmal spike activity, 24 +/- 1 min (N = 20) after administration of pilocarpine, and continued uninterrupted for more than 3 h. Kainic acid (10 mg/kg)-induced status epilepticus developed approximately 60 min after initial spike activity, 96 +/- 3 min (N = 7) after kainate administration, and continued for 0.5 h. Thus, the interval of intermittent seizure activity and the duration of status epilepticus differed markedly between these two models. The potentiation by lithium (3 meq/kg) of the convulsant effect of cholinergic agonists was found to be 10 to 13-fold for two direct-acting cholinomimetics, pilocarpine and arecoline, whereas the convulsant effect of the indirect-acting agonist, physostigmine, was potentiated by 50%. The full proconvulsant effect of lithium lasted from 2 to 24 h after a single acute treatment (3 meq/kg). The dose response of the proconvulsant effect of lithium was determined and the EC50 of lithium was approximately 1.5 meq/kg when pilocarpine (30 mg/kg) was administered 20 h later. Chronic treatment with lithium for 4 weeks potentiated the convulsant effect of pilocarpine by more than 26-fold. These results demonstrated that both acute and chronic administration of lithium enhance cholinergic function in vivo. Potentiation of cholinergic function by lithium may play a role in the therapeutic action of lithium in affective disorders.