Assessment of low level whole-body soman vapor exposure in rats.
We evaluated biochemical and behavioral effects of single, low-level exposures to the chemical warfare nerve agent soman (GD). Male Sprague-Dawley rats were trained on a variable-interval, 56-sec schedule of food reinforcement (VI56). The schedule specifies that a single lever press, following an average interval of 56 s, produces food reinforcement (i.e., a single food pellet). After training, rats received a single 60 min exposure to soman vapor at concentrations of 1.0-7.0 mg/m(3), or air control (n=8 for each treatment condition). Blood was sampled before and after the exposure. Following exposures, performance on the VI56 was evaluated for approximately 11 weeks. Additionally, the acquisition and maintenance of a radial-arm maze (RAM) spatial memory task were evaluated in the same subjects during the same 11-week period. Soman exposures produced miosis in all subjects but were otherwise essentially asymptomatic. That is, no convulsions or major signs of toxicity were observed in any subjects, a result consistent with a low-level concentration. Soman exposures produced significant and concentration-dependent decreases in circulating acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity. Soman exposures also produced concentration-dependent levels of regenerated soman in plasma and red blood cell fractions that served to verify the systemic exposure and estimate the total body burden. Soman exposure did not disrupt performance on the VI56 schedule as responding was maintained at pre-exposure levels throughout the 11-week period in all treatment groups. All subjects acquired, and maintained, performance on the RAM task and no significant differences were observed as a result of soman exposure. That is, soman-exposed rats learned the RAM task at the same general rate and to the same general level of accuracy as air-control rats. No delayed effects from exposures were observed. These results demonstrate that, in rats, single exposures to soman vapors at levels that produce substantial AChE and BChE inhibition, but below those producing convulsions and other severe clinical signs of toxicity, may not produce observable effects on the performance of a previously learned task or the acquisition of a new task.
Genovese
Raymond F
RF
Division of Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910-7500, USA. Raymond.Genovese@US.ARMY.MIL
Benton
Bernard J
BJ
Johnson
Christina C
CC
Jakubowski
E Michael
EM
D000110:Acetylcholinesterase / Q000097:blood; D000818:Animals; D002091:Butyrylcholinesterase / Q000097:blood; D002619:Chemical Warfare Agents / Q000493:pharmacokinetics* / Q000633:toxicity*; D003216:Conditioning, Operant / Q000187:drug effects; D019570:Inhalation Exposure; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012999:Soman / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity
D002619:Chemical Warfare Agents; D012999:Soman; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase