D-1 dopamine agonist administration reduces the threshold for convulsions produced by pilocarpine

Focal, limbic seizures were produced by systemically administered pilocarpine (200 mg/kg, i.p.); as previously described this dose produces limbic stereotypies but neither convulsions nor seizure-related brain damage. The pretreatment, 5 minutes prior pilocarpine, with the D-1 agonist SKF 38393 (-ED50 = 1 mg/kg; i.p.) induced convulsions similar to those produced by a higher, convulsant dose of pilocarpine. On the other hand, the pretreatment with the D-2 agonist LY 171555 failed to induce convulsions. The D-1 receptor antagonist SCH 23390 prevented the convulsions induced by SKF 38393 plus pilocarpine (200 mg/kg). This study indicates that D-1, but not D-2, receptor stimulation converts subconvulsant doses of pilocarpine into convulsant ones.