Antagonism of intrastriatal and intravenous kainic acid by 1-nuciferine: Comparison with various anticonvulsants and gabamimetics

Abstract 1-Nuciferine has been proposed as an antagonist of kainic acid (KA) and/or glutamate on the basis of iontophoretic experimental results. Its effectiveness against KA-induced destruction of rat striatal cholinergic neurons was therefore evaluated and compared with that of diazepam, phenobarbital, baclofen, haloperidol, and related substances. Drugs were administered intraperitoneally before and after intrastriatal microinjection of KA (0.5–1.5 μg), and choline acetyltransferase activity in striatum was assessed 24 hr later. Among the substances tested, only 1-nuciferine attenuated KA-induced depletions of striatal choline acetyltransferase. This effect was not secondary to anticonvulsant activity, because (a) 1-nuciferine did not block metrazol-, maximal electroshock-, or intravenous KA-induced seizures, and (b) anticonvulsants such as phenobarbital and diazepam, which are effective in these procedures, failed to modify KA-induced striatal neurotoxicity. 1-Nuciferine antagonized certain other neurological effects of intravenous KA, but antagonism was also seen with some of the other drugs tested. Intrastriatal microinjection of KA and/or glutamate may offer a means to detect selective antagonism of KA and/or glutamate, as distinguished from simple anticonvulsant activity.