Modification of kainate-induced behavioral and electrographic seizures following inhibition of nitric oxide synthase in mice.
We assessed the effects of N(omega)-nitro-L-arginine-methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), on behavioral and electrographic seizures elicited in mice by convulsant doses of kainate. In Expt. 1, L-NAME dose-dependently potentiated the convulsant effects of kainate (44 mg/kg s.c.), transforming long-latency clonic convulsions into short-latency fits of wild-running, and increased the incidence of kainate-induced mortality. The proconvulsant effects of L-NAME (5 mg/kg i.p.) did not reflect shortened latency to kainate-induced epileptiform afterdischarge recorded via electrodes chronically implanted into the hippocampus, amygdala, frontal cortex or mesencephalic reticular formation (Expt. 2). We also observed a dramatic uncoupling of behavioral and electrographic seizures in mice treated with L-NAME 30 min prior to kainate: 4/6 mice treated with L-NAME failed to express afterdischarge from any of the sites assessed during fits of wild-running. The proconvulsant effects of L-NAME were dependent on the route of administration of kainate, as the inhibitor of NOS failed to alter behavioral (clonic) or electrographic seizures elicited by intrahippocampal kainate (1 nmol, Expt. 3) yet shortened latency to fits of wild-running following i.c.v. kainate (1 nmol, Expt. 4) and reduced the dose of systemic kainate required for either clonic convulsions or wild-running (Expt. 5). The observations that L-NAME potentiates kainate-induced wild-running but not necessarily clonus suggest the involvement of tectopontine mechanisms.
Kirkby
R D
RD
Neuronal Excitability Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1408, USA.
Forbes
R A
RA
Subramaniam
S
S
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus; D007276:Injections, Intraventricular; D007608:Kainic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008845:Microinjections; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control* / Q000523:psychology
D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D019001:Nitric Oxide Synthase; D007608:Kainic Acid; D019331:NG-Nitroarginine Methyl Ester