Bimodal effects of dopamine D2 receptor agonists on zero Mg(2+)-induced epileptiform activity in the rat cingulate cortex slice.
A previous study demonstrated a dopamine D1 receptor-dependent inhibition of zero Mg(2+)-induced epileptiform discharges in the rat cingulate cortex slice suspended in a grease-gap bath. This investigation considers the role of dopamine D2 receptors in the modulation of paroxysmal activity in this in vitro model. Some 123 of 143 slices exhibited spontaneous paroxysmal depolarizations, which in 105 cases were accompanied by secondary depolarizing after-potentials (SDAPs). In 43.5% of slices tested, dopamine preferentially and irreversibly facilitated SDAP production at low bath concentrations (1-100 microM), but at concentrations > 100 microM suppressed all components of the epileptiform responses. Similar dose-related bimodal responses were obtained with the D2 agonists LY 171555, PHNO and 7-OH-DPAT, but not with lisuride or RU 24213, which were exclusively inhibitory. The excitatory response to LY 171555 was attenuated by the D2 antagonist raclopride (2 microM), but not by the D1 antagonist SCH 39166 (0.5 microM). On the other occasions, the sole effect of dopamine (56.5% of slices) and the other D2 agonists, was to preferentially suppress SDAP number at low concentrations (1-100 microM) and to suppress all parameters of the epileptiform response at higher concentrations. The inhibitory effect of the D2 agonist LY 171555 on SDAP formation was paradoxically attenuated by the D1 antagonist SCH 39166, but not by the D2 antagonist raclopride. These results support the notion that dopamine can modulate epileptiform activity differentially, through its actions at D1 and D2 receptors. The possibility that these effects of dopamine may be mediated indirectly is discussed.
Alam
A M
AM
Department of Pharmacology, School of Pharmacy, London, UK.
Starr
M S
MS
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004827:Epilepsy; D004873:Ergolines / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D006179:Gyrus Cinguli / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008090:Lisuride / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D010078:Oxazines / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology; D019257:Quinpirole; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000502:physiology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D001552:Benzazepines; D065127:Dopamine D2 Receptor Antagonists; D004873:Ergolines; D010078:Oxazines; D010627:Phenethylamines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013764:Tetrahydronaphthalenes; C058081:ecopipam; D019257:Quinpirole; C042631:naxagolide; C016868:N-n-propyl-N-phenylethyl-4(3-hydroxyphenyl)ethylamine hydrochloride; D008090:Lisuride; D008274:Magnesium; C031349:7-hydroxy-2-N,N-dipropylaminotetralin