Abnormal expression of neuronal nitric oxide synthase triggers limbic seizures and hippocampal damage in rat

Biochem Biophys Res Commun. 2002 Feb 22;291(2):255-60. doi: 10.1006/bbrc.2002.6424.


Administration of tacrine (5 mg/kg ip), an anticholinesterase agent, in rats pretreated (24 h beforehand) with lithium chloride (LiCl; 12 mEq/kg ip) provides a useful experimental model to study limbic seizures and delayed hippocampal damage. Here we report Western blotting evidence demonstrating that in rat LiCl and tacrine enhance the expression of neuronal nitric oxide synthase (nNOS), but not eNOS, enzyme protein in the hippocampus during the preconvulsive period and this triggers seizures and hippocampal damage. In fact, systemic administration of 7-nitro indazole (7-NI; 50 mg/kg given ip 30 min before tacrine), a selective inhibitor of nNOS, prevented the expression of motor and electrocortical (ECoG) seizures and abolished neuronal cell death in the hippocampus. A lower dose (5 mg/kg ip) of 7-NI was ineffective. In conclusion, the present data support a role for abnormal nNOS expression in the mechanism which triggers limbic seizures and delayed excitotoxic damage in the hippocampus of rat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cholinesterase Inhibitors / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Hippocampus / enzymology
  • Hippocampus / pathology*
  • Indazoles / pharmacology
  • Lithium Chloride / antagonists & inhibitors
  • Male
  • Neuroprotective Agents / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / biosynthesis*
  • Nitric Oxide Synthase Type I
  • Rats
  • Rats, Wistar
  • Seizures / enzymology*
  • Seizures / etiology*
  • Seizures / pathology
  • Tacrine / antagonists & inhibitors


  • Cholinesterase Inhibitors
  • Enzyme Inhibitors
  • Indazoles
  • Neuroprotective Agents
  • Tacrine
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type I
  • Nos1 protein, rat
  • Lithium Chloride
  • 7-nitroindazole