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Dopamine control of seizure propagation: Intranigral dopamine D1 agonist SKF‐38393 enhances susceptibility of seizures
Author(s) -
Turski Waldemar A.,
Cavalheiro Esper A.,
Ikonomidou Chrysanthy,
Bortolotto Zuner A.,
Klockgether Thomas,
Turski Lechoslaw
Publication year - 1990
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.890050205
Subject(s) - agonist , sch 23390 , pilocarpine , chemistry , dopamine , substantia nigra , pharmacology , dopamine agonist , striatum , quinpirole , endocrinology , medicine , epilepsy , dopaminergic , neuroscience , receptor , psychology , biochemistry
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 SKF‐38393 into the substantia nigra enhances the susceptibility of rats to seizures, with and ED 50 fo 20 pmol (range 13‐31 pmol), converting subconvulsant doses of the cholinergic agonist pilocarpine (200 mg/kg; i.p.) into convulsant ones. The proconvulsant action of SKF‐38393 was reversed by blocking D 1 ‐mediated transmission in the substantia nigra with the D 1 antagonist SCH‐23390. The D 2 agonist LY‐171555 did not modulate the threshold for limbic seizures when injected into the substantia nigra. In the striatum, the D 2 agonist LY‐171555 protected rats against limbic seizures induced by systemic administration of pilocarpine (380 mg/kg; i.p.), with an ED 50 of 2 pmol (range 1.4–2.8 pmol). The anticonvulsant action of LY‐171555 in the striatum was reversed by haloperidol. The D 1 agonist SKF‐38393 did not affect pilocarpine seizures following administration into the striatum. Systemic administration of DAergic drugs showed that the D 1 agonist SKF‐38393 decreased the threshold for pilocarpine seizures, with an ED 50 of 0.81 mg/kg (range 0.45–1.47 mg/kg), whereas the D 2 agonist LY‐171555 had no effect on susceptibility of rats to pilocarpine. Thr proconvulsant action of SKF‐38393 was blocked by the D 1 antagonist SCH‐23390. 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.