Development of Behavioral Toxicology Methodology for Interactive Exposure Regimens

摘要

This program was conducted to investigate methodology for determining effects on performance of exposure to inhaled substances alone or in combination with fatigue or heat stress. Carbon monoxide (CO) was used as a prototypic chemical and rats as the animal model. A series of preliminary experiments were conducted to establish the appropriate test parameters, exposure method, and effects on carboxyhemoglobin. All studies were conducted using operant schedules of reinforcement with food as the reinforcer. Performance on a variable ratio-fixed ratio schedule was disrupted during a 1-hr exposure to 1250 ppm CO and by forced swimming regardless of CO concentration. Lower CO concentrations had no effect. Performance on a fixed ratio-fixed ratio schedule was disrupted during 75 min exposures to CO at 700 ppm but not at 200 or 450 ppm. Forced swimming and a high environmental temperature (30.5 C) also impaired performance on this schedule. There were no significant interactions for CO and swim stress; however, the combination of 450 ppm and heat stress produced a greater impairment than predicted by the separate effects of these conditions. Testing on a reaction time task indicated increased reaction times at 450 ppm and a trend in this direction at 700 ppm. Responding in this task was lowered by 700 and 450 ppm but heat affected neither reaction time nor responding.