Dopaminergic modulation of lithium/pilocarpine-induced status epilepticus in rats.

The effects of selective dopaminergic agonists and antagonists on epileptic activity were tested in rats using the lithium/pilocarpine seizure model. Systemic administration of the D1 agonist SKF-38,393 reduced the latency of onset of forelimb clonus with rearing, whereas the D1 antagonist SCH-23,390 and the D2 agonist B-HT 920 prevented the convulsive activity in a dose-dependent manner. Mixed agonists like apomorphine offered partial protection. Haloperidol (D1, D2 blocker, with antimuscarinic property) reduced the threshold for convulsions. The effects of SKF-38,393 and B-HT 920 could be partially blocked by pretreating the rats with SCH-23,390 and sulpiride, respectively. Neither D1 nor D2 antagonists could alter the limbic stereotypies induced by lithium/pilocarpine. These results indicate that dopamine receptor subtypes exert opposite effects on the regulation of convulsive activity. Lipid peroxidation levels (MDA formed) in rat brain homogenates were found to be concomitant with the development of epileptiform activity.