Memory impairment after soman intoxication in rat: correlation with central neuropathology. Improvement with anticholinergic and antiglutamatergic therapeutics

Neurotoxicology. 1999 Aug;20(4):535-49.

Abstract

The effects of soman, a potent irreversible inhibitor of acetylcholinesterase, on central neuropathology in rats were studied in relation with subsequent spatial memory impairments. In a first step, it was found that, without treatment, neuropathology and learning impairment were observed only in rats which experienced convulsions. Then, treatment consisting of atropine sulfate, and/or TCP and/or NBQX was administered to intoxicated animals at infraanticonvulsant doses to obtain a graded subsequent neuropathology and to appreciate an eventual relation between neuropathology and spatial memory impairment. Thus, a correlation between neuropathology in the hippocampal CA1 region and spatial learning performance was found, the degradation of performance of rat being directly related to the amplitude of their neural damage. A threshold was emphasized : below a certain degree of neural loss, no memory impairment was found. Only treatment with tritherapy (atropine + TCP + NBQX) was able to improve the different parameters of spatial learning, despite no effect on the convulsions of the animals.

MeSH terms

  • Animals
  • Antidotes / pharmacology
  • Atropine / pharmacology
  • Behavior, Animal / drug effects
  • Cholinergic Antagonists / pharmacology
  • Convulsants / toxicity
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Hippocampus / drug effects*
  • Hippocampus / pathology
  • Male
  • Maze Learning / drug effects
  • Memory Disorders / chemically induced*
  • Neuroprotective Agents / pharmacology
  • Phencyclidine / analogs & derivatives*
  • Phencyclidine / pharmacology
  • Quinoxalines / pharmacology*
  • Rats
  • Rats, Wistar
  • Soman / toxicity*
  • Spatial Behavior / drug effects
  • Survival Rate
  • Time Factors

Substances

  • Antidotes
  • Cholinergic Antagonists
  • Convulsants
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Neuroprotective Agents
  • Quinoxalines
  • 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
  • Atropine
  • tenocyclidine
  • Soman
  • Phencyclidine