Dopaminergic modulation of pilocarpine-induced motor seizures in the rat: the role of hippocampal dopamine D1 receptors.
The present study addressed the role of dopamine D1 receptors in pilocarpine-induced motor seizures in rats. Bilateral pretreatment of the hippocampus with the D1 agonist SKF 38393 (0.1-5 micrograms) did not alter the animals' sensitivity to a threshold (200 mg/kg i.p.) or fully convulsant dose (600 mg/kg i.p.) of pilocarpine, as compared to hippocampal saline-treated controls. Similarly, direct injection of pilocarpine (200 micrograms per side) into both hippocampi elicited low level seizure activity that was not modified by SKF 38393, either coadministered (2 micrograms per side) or injected systemically (30 mg/kg i.p.). On the other hand, intrahippocampal microinjections of the D1 antagonist, SCH 23390 (2 micrograms per side), whilst unable to prevent epileptogenesis to 600 mg/kg pilocarpine, delayed the onset of seizures and reduced their severity. These results suggest that hippocampal dopamine lowers the seizure threshold by activating D1 receptors, an effect which is only disclosed by D1 receptor blockade and is not surmountable by additional D1 stimulation.
Alam
A M
AM
Department of Pharmacology, School of Pharmacy, London, UK.
Starr
M S
MS
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D010862:Pilocarpine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects*; D012640:Seizures / Q000139:chemically induced* / Q000517:prevention & control
D001552:Benzazepines; D017447:Receptors, Dopamine D1; D010862:Pilocarpine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine