Nerve agents behavioral effects

Exposures to nerve agents have also been associated with subtle neurological effects manifested as altered EEGs (Metcalf and Holmes, 1969 Burchfiel et al., 1976 Duffy et al., 1979 Duffy and Burchfiel, 1980) and psychological changes (Sidell, 1992). The reported EEG abnormalities have not been correlated with behavioral or physiological parameters. 

It should be further noted that the effects of nerve agents on GABAergic transmission in the CNS may have imph-cations for behavioral effects in laboratory animals and humans, and may also contribute to the induction of convulsions at higher doses (Bakshi et al, 2000). Nevertheless, given the present undefined application of non-cholinergic data to whole-body estimations, reliance on the primary assumption of AChE action is consistent with recognized opinion (Bakshi et al, 2000). 

II. THE METHODS USED TO EVALUATE BEHAVIORAL EFFECTS OF NERVE AGENTS... 

IV. CHRONIC BEHAVIORAL EFFECTS OF SINGLE OR REPEATED LOW-LEVEL EXPOSURE TO NERVE AGENTS... 

Hartgraves, S.L., Murphy, M.R. (1992). Behavioral effects of nerve agents. In Chemical Warfare Agents (S. Somani, ed.). Academic Press, New York. 

The pharmacologic and toxicologic effects of the nerve agents are dependent on their stability, rates of absorption by the various routes of exposure, distribution, ability to cross the blood-brain barrier, rate of reaction and selectivity with the enzyme at specific foci, and their behavior at the active site on the enzyme. 

Although there is a lack of information on the general toxicological effects of low-level, and suble-thal repeated exposures, there are studies on the behavioral effects of such exposures to nerve agents in animals free of observed signs of intoxication. These were conducted in an effort to determine whether behavioral studies can provide markers of early neurotoxicity that are more sensitive than neurochemical and neuropathological changes. 

Small doses of nerve agents in animals can produce tolerance in additional to their classical cholinergic effects. In rats, acute administration of nerve agents in subconvulsive doses produced tumors and hind-limb adduction. In animals, nerve agents can also cause behavioral as well as cardiac effects. 

The binding of the nerve agent to the enzyme is considered irreversible unless removed by therapy. The accumulation of acetylcholine in the peripheral nervous system and central nervous system (CNS) leads to depression of the respiratory center in the brain, followed by peripheral neuromuscular blockade causing respiratory depression and death. The pharmacologic and toxicologic effects of the nerve agents are dependent on their stability, rates of absorption by the various routes of exposure, distribution, ability to cross the blood-brain barrier, rate of reaction and selectivity with the enzyme at specific foci, and their behavior at the active site on the enzyme. 

Cerasoli, D. M., Lenz, D. E. (2002/this issue). Nerve agent bioscavengers Protection with reduced behavioral effects. Military Psychology, 14, 121—143. 

This cluster of CNS and behavioral effects of nerve agents is consistent with what is known about the role of acetylcholine and cholinergic neurons within the brain. Central cholinergic circuits are involved in both cognition and short-term... 

Nerve Agent Bioscavengers Protection With Reduced Behavioral Effects... 

---