Memory impairment after soman intoxication in rat: correlation with central neuropathology. Improvement with anticholinergic and antiglutamatergic therapeutics.
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.
Filliat
P
P
Unité de Neuropharmacologie, Centre de Recherches du Service de Santé des Armées Emile Parde, La Tronche, France. 100437,201@compuserve.com
Baubichon
D
D
Burckhart
M F
MF
Pernot-Marino
I
I
Foquin
A
A
Masqueliez
C
C
Perrichon
C
C
Carpentier
P
P
Lallement
G
G
D000818:Animals; D000931:Antidotes / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D018680:Cholinergic Antagonists / Q000494:pharmacology; D003292:Convulsants / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012999:Soman / Q000633:toxicity*; D013037:Spatial Behavior / Q000187:drug effects; D015996:Survival Rate; D013997:Time Factors
D000931:Antidotes; D018680:Cholinergic Antagonists; D003292:Convulsants; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D001285:Atropine; C012058:tenocyclidine; D012999:Soman; D010622:Phencyclidine