The role of nitric oxide in focally-evoked limbic seizures.
The deep rostral piriform cortex contains a site (area tempestas) in which focal application of picomole amounts of bicuculline, a GABA antagonist, triggers limbic motor seizures which are dependent upon activation of both N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyloxole-4-proprionate subtypes of glutamate receptors. In the present study we determined whether nitric oxide can influence the local modulation of seizure initiation by bicuculline. Nitric oxide and the nitric oxide precursor L-arginine, alone or in combination with low doses of bicuculline were focally administered into the area tempestas of rats. While nitric oxide alone had no significant convulsant effect, L-arginine 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 prevented by focal pretreatment with an inhibitor of nitric oxide synthesis, N-nitro-L-arginine methyl ester. However, N-nitro-L-arginine methyl ester did not attenuate the convulsant effect of bicuculline or kainate alone when focally administered into area tempestas. The data demonstrate that exogenously applied nitric oxide or its precursors can enhance seizure triggering activity. However, the data also indicate that L-arginine-nitric oxide pathway does not normally contribute to seizure expression from area tempestas, as N-nitro-L-arginine methyl ester alone did not attenuate focally-evoked seizures.
Proctor
M R
MR
Department of Pharmacology, Georgetown University Medical Center, Washington, D.C., USA.
Fornai
F
F
Afshar
J K
JK
Gale
K
K
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D008032:Limbic System / Q000503:physiopathology*; D008297:Male; D009207:Myoclonus / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000503:physiopathology*
D004791:Enzyme Inhibitors; D018756:GABA Antagonists; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D001640:Bicuculline