Abstract
1. To study the influence of antidotes on low-level sarin-induced impairment of cognitive functions, the rats were exposed to three various low concentrations of sarin (LEVEL 1-3) for 60 minutes in the inhalation chamber. In addition, one group of rats was exposed to LEVEL 2 of sarin repeatedly. 2. Testing of cognitive functions was carried out using the Y-maze evaluating learning and spatial memory. The correct averse behavior of sarin-exposed rats in the Y-maze was tested several times within four weeks following sarin inhalation exposure and antidotal treatment to look for any cognitive impairments. 3. The results were compared to the Y-maze performance of sarin-exposed rats without antidotal treatment and control rats exposed to pure air instead of sarin with or without antidotal treatment. While antidotal treatment was able to eliminate a short-term deficiency in the Y-maze performance in rats exposed to the LEVEL 1 of sarin, a significant decrease in the Y-maze performance in rats exposed to sarin at the LEVEL 2 and 3 was only shortened. Sarin-induced spatial memory impairments in rats exposed repeatedly to sarin at the LEVEL 2 was also shortened when rats were treated following each sarin inhalation exposure. 4. The findings confirm that antidotes currently used for nerve agent poisonings are beneficial for the treatment of rats singly or repeatedly exposed to non-convulsive symptomatic or even clinically asymptomatic concentrations of sarin.
Highlights
The potential for the exposure to highly toxic organophosphorus compounds (OPs), called nerve agents, exists on the battlefield (e.g. Iran-Iraq war) as well as in a civilian sector as a threat by a terrorist group (e.g. Tokyo subway incident – 16) or as an accident as part of current demilitarization efforts
The correct averse behavior of sarin-exposed rats in the Y-maze was tested several times within four weeks following sarin inhalation exposure and antidotal treatment to look for any cognitive impairments
The results were compared to the Y-maze performance of sarin-exposed rats without antidotal treatment and control rats exposed to pure air instead of sarin with or without antidotal treatment
Summary
The potential for the exposure to highly toxic organophosphorus compounds (OPs), called nerve agents, exists on the battlefield (e.g. Iran-Iraq war) as well as in a civilian sector as a threat by a terrorist group (e.g. Tokyo subway incident – 16) or as an accident as part of current demilitarization efforts. The irreversible binding to and subsequent inactivation of acetylcholinesterase (AChE, EC 3.1.1.7) in the central as well as peripheral nervous system allowing accumulation of acetycholine (ACh) and excessive stimulation of postsynaptic cholinergic receptors is generally believed to be the major mechanism of poisoning. The overstimulation of central cholinergic system is followed by the activation of other neurotransmitter systems including glutamate receptors leading to the increase in extracellular levels of the excitatory amino acid glutamate, a major excitotoxin mediating central neurotoxicity of OPs [14,24]. Behavioral alterations and impairments of cognitive functions were found following acute exposure to OPs in the absence of any classic signs of cholinergic toxicity [10,21]
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