Behavioral, neurochemical and physiological effects of repeated exposures to subsymptomatic levels of the anticholinesterase, soman.

Abstract

The present experiments were designed to study behavioral, neurochemical and physiological effects of repeated exposure to subsymptomatic levels of the anticholinesterase, soman. Sprague-Dawley rats were placed on a soman regimen of 35 micrograms kg-1 (0.3 log10 units below the LD50) which consisted of daily injections SC for the first three days, followed by the same dose three times per week for a total of 11 injections (22 days). There were no significant differences in pretreatment baselines between soman-treated and saline control animals for any of the variables measured. Some basic physiological processes, i.e., caloric intake and body fluid balance, and behavioral functions associated with aversive reinforcement (e.g., conditioned avoidance response) were not affected by the soman regimen. Core body temperature showed an early hypothermia and later developed tolerance. Nociceptive sensory and perceptual thresholds were elevated (hypoalgesia) and remained so throughout the treatment. Temporal perception (as evidenced in fixed interval responding) was significantly impaired initially, but tolerance developed as the duration of the regimen increased. Tolerance was also evident in measures of general activity and cognitive functions. The process of tolerance development proceeded when brain AChE activity was depressed and stable, indicating that some other process(es) must have been involved. The results of the present series of experiments show quite clearly that exposure to the antiChE, soman, at subsymptomatic levels can produce differential effects on enzymatic, physiological and behavioral functions, i.e., some of these functions may be affected while others are not. Moreover, effects when they do appear may also differ in that some may persist during the duration of the exposure, while others may appear initially and then disappear as tolerance develops.