Abstract
The involvement of dopamine (DA) in human and experimental epilepsy has been discounted as DAergic drugs have little effect on convulsions. This work presents evidence that bilateral microinjection of the DA D~1~ agonist SKFβ38393 into the substantia nigra enhances the susceptibility of rats to seizures, with and ED~50~ fo 20 pmol (range 13β31 pmol), converting subconvulsant doses of the cholinergic agonist pilocarpine (200 mg/kg; i.p.) into convulsant ones. The proconvulsant action of SKFβ38393 was reversed by blocking D~1~βmediated transmission in the substantia nigra with the D~1~ antagonist SCHβ23390. The D~2~ agonist LYβ171555 did not modulate the threshold for limbic seizures when injected into the substantia nigra. In the striatum, the D~2~ agonist LYβ171555 protected rats against limbic seizures induced by systemic administration of pilocarpine (380 mg/kg; i.p.), with an ED~50~ of 2 pmol (range 1.4β2.8 pmol). The anticonvulsant action of LYβ171555 in the striatum was reversed by haloperidol. The D~1~ agonist SKFβ38393 did not affect pilocarpine seizures following administration into the striatum. Systemic administration of DAergic drugs showed that the D~1~ agonist SKFβ38393 decreased the threshold for pilocarpine seizures, with an ED~50~ of 0.81 mg/kg (range 0.45β1.47 mg/kg), whereas the D~2~ agonist LYβ171555 had no effect on susceptibility of rats to pilocarpine. Thr proconvulsant action of SKFβ38393 was blocked by the D~1~ antagonist SCHβ23390. These results suggest that DA differentially modulates seizure threshold in the forbrain acting via D~1~ mechanisms in the substantia nigra and D~2~ mechanisms in the striatum.