Analysis of the convulsant-potentiating effects of lithium in rats

Lithium pretreatment of rats has previously been shown to potentiate the convulsant effects of cholinomimetic drugs, such as pilocarpine. The first objective of this project was to determine if lithium also potentiates seizures induced by other classes of drugs. Lithium pretreatment of rats did not affect seizure activity induced by administration of N-methyl-d-aspartate, kainic acid, bicuculline, or pentylenetetrazole. This suggests that the proconvulsant effect of lithium is largely selective for cholinomimetics. A second series of experiments investigated possible mechanisms of the lithium potentiation of pilocarpine-induced seizures. The α₂-adrenergic receptor agonist clonidine suppressed seizure development, and the antagonist idazoxan enhanced the onset of seizures, suggesting that endogenous norepinephrine provides anticonvulsant properties. Administration of the norepinephrine depleter DSP-4 potentiated pilocarpine-induced seizures. These results suggest that the previously reported impairment of noradrenergic function by lithium may play a role in its potentiation of cholinomimetic-induced seizures.