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.