Proconvulsant effect of SKF 38393 mediated by nigral D1 receptors

This study investigated the hypothesis that the proconvulsant action of systemically applied dopamine D1 receptor stimulants is mediated by D1 receptors in the substantia nigra. Rats were equipped with bilateral stainless steel guide cannulas under halothane anaesthesia, to allow drugs to be injected into both nigras of conscious, unrestrained animals 7-14 days later. Bilateral intranigral administration of saline, together with a subconvulsant dose of pilocarpine (200 mg/kg), produced no convulsions in 14 rats. By contrast, intranigral SKF 38393 (2.5 micrograms) and pilocarpine (200 mg/kg) caused 18/22 rats to convulse. This proconvulsant action of SKF 38393 was completely attenuated by pretreatment with SCH 23390 (0.25 mg/kg). SCH 23390 (1 microgram) delivered into both nigras reduced the number of rats convulsing in response to 600 mg/kg pilocarpine (7/15, one fatally) as compared to saline-injected controls (12/13, eight fatally). These results indicate that dopamine D1 receptors in the substantia nigra (pars reticulata) mediate a proconvulsant action of dopamine, which is opposite to the anticonvulsant effect of the amine at striatal D2 receptors.