THE ROLE OF NITRIC-OXIDE IN FOCALLY-EVOKED LIMBIC SEIZURES

The deep rostral piriform cortex contains a site (area tempestas) in w hich focal application of picomole amounts of bicuculline, a GABA anta gonist, triggers limbic motor seizures which are dependent upon activa tion of both N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methylox ole-4-proprionate subtypes of glutamate receptors. In the present stud y we determined whether nitric oxide can influence the local modulatio n of seizure initiation by bicuculline. Nitric oxide and the nitric ox ide precursor L-arginine, alone or in combination with low doses of bi cuculline were focally administered into the area tempestas of rats. W hile nitric oxide alone had no significant convulsant effect, L-argini ne alone (30-240 nmol) induced brief myoclonic episodes. Nitric oxide (0.7 nmol) and L-arginine (30 nmol) markedly potentiated the seizures evoked by a low dose of bicuculline. The effect of L-arginine was prev ented by focal pretreatment with an inhibitor of nitric oxide synthesi s, N-nitro-L-arginine methyl eater. However, N-nitro-L-arginine methyl ester did not attenuate the convulsant effect of bicuculline or kaina te alone when focally administered into area tempestas. The data demon strate that exogenously applied nitric oxide or its precursors can enh ance seizure triggering activity. However, the data also indicate that L-arginine-nitric oxide pathway does not normally contribute to seizu re expression from area tempestas, as N-nitro-L-arginine methyl ester alone did not attenuate focally-evoked seizures. Copyright (C) 1996 IB RO. Published by Elsevier Science Ltd.