Comparative sensitivity of neurobehavioral tests for chemical screening

Guidelines for conducting neurobehavioral tests of motor activity, schedule-controlled operant performance, and a functional observational battery (FOB) were published by the U.S. EPA Office of Toxic Substances (1985). We have utilized a specific FOB protocol in conjunction with motor activity measured in a figure-eight maze and performance maintained under a fixed-interval schedule of reinforcement to determine the acute effects of chemicals which produce different syndromes of intoxication in rats (chlordimeform, carbaryl, pentobarbital, triadimefon, nicotine, and 3-acetyl pyridine). The results showed that for each compound there was a substantial degree of overlap in the dose range of effectiveness across the different tests. In all cases, however, the lowest effective dose identified using the FOB was equal to or less than that provided by motor activity and operant tests. For most compounds, motor activity and operant performance were equally sensitive. Nicotine and triadimefon, however, increased the rate of operant responding at lower doses than those that affected motor activity. The time course of each chemical appeared similar across tests with one exception. 3-Acetyl pyridine produced clear effects in the FOB throughout testing (up to three weeks) whereas recovery was evident within one week using motor activity and operant performance. FOB and motor activity testing can be easily integrated into ongoing toxicity studies. On the other hand, the traditional approach to testing the effects of chemicals on operant performance requires prior food or water deprivation, and time for training the animals and establishing a stable level of performance. In the context of hazard identification (i.e., testing for the effects of unknown chemicals) the FOB and motor activity may be expected to adequately detect neurotoxicity. Operant performance may be more valuable in characterizing the actions of identified neurotoxicants.