title: Galantamine counteracts development of learning impairment in guinea pigs exposed to the organophosphorus poison soman: clinical significance.
abstract: Galantamine, a drug used to treat Alzheimer's disease, protects guinea pigs against the acute toxicity and lethality of organophosphorus (OP) compounds, including soman. Here, we tested the hypothesis that a single exposure of guinea pigs to 1xLD50 soman triggers cognitive impairments that can be counteracted by galantamine. Thus, animals were injected intramuscularly with saline (0.5 ml/kg) or galantamine (8 mg/kg) and 30 min later injected subcutaneously with soman (26.3 μg/kg) or saline. Cognitive performance was analyzed in the Morris water maze (MWM) four days or three months after the soman challenge. Fifty percent of the saline-injected animals that were challenged with soman survived with mild-to-moderate signs of acute toxicity that subsided within a few hours. These animals showed no learning impairment and no memory retention deficit, when training in the MWM started four days post-soman challenge. In contrast, animals presented significant learning impairment when testing started three months post-challenge. Though the magnitude of the impairment correlated with the severity of the acute toxicity, animals that presented no or only mild signs of toxicity were also learning impaired. All guinea pigs that were treated with galantamine survived the soman challenge with no signs of acute toxicity and learned the MWM task as control animals, regardless of when testing began. Galantamine also prevented memory extinction in both saline- and soman-challenged animals. In conclusion, learning impairment develops months after a single exposure to 1xLD50 soman, and galantamine prevents both the acute toxicity and the delayed cognitive deficits triggered by this OP poison.
authors.affiliation: Division of Translational Toxicology, Department Epidemiology and Public Health, University of Maryland School of Medicine, 10 S. Pine St. Suite 900, Baltimore, MD 21210, USA. jmamczarz@umaryland.edu
authors.forename: Jacek
authors.initials: J
authors.lastname: Mamczarz
authors.forename: Girish S
authors.initials: GS
authors.lastname: Kulkarni
authors.forename: Edna F R
authors.initials: EF
authors.lastname: Pereira
authors.forename: Edson X
authors.initials: EX
authors.lastname: Albuquerque
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control* / Q000523:psychology; D004195:Disease Models, Animal; D005108:Extinction, Psychological / Q000187:drug effects; D005260:Female; D005702:Galantamine / Q000494:pharmacology*; D006168:Guinea Pigs; D007928:Lethal Dose 50; D018782:Maze Learning / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018697:Nootropic Agents / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D012999:Soman / Q000633:toxicity*; D013997:Time Factors
chemical_list: D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D005702:Galantamine; D012999:Soman