Behaviors in the Home Cage Reveal Toxicity: Recent Findings and Proposals for the Future

Abstract

Nervous system impairment is prominent among signs of chemical toxicity in humans and animals, yet evaluation of behavioral and neurologic responses is seldom included in premarket screening. The sensitivity and validity of automatically recorded rodent locomotor activity, whether inside or outside of the home cage, justifies its inclusion in first-tier testing. Home cage behaviors are studied in the toxicologic laboratory using quantitative techniques from behavioral neuroscience. A practical, noninvasive, automated system was developed and validated at New York University, in accord with Federal guidelines for testing neurotoxicity. Effects of neurotoxicants on motor activity, eating, drinking, and the daily cycle of rest-activity indicate sensitivity to a variety of chemicals as well as new avenues to the understanding of mechanisms of toxicity. The rat's pattern of nocturnal activity is particularly sensitive to neurotoxicants and thus deserves additional attention. The coefficient of variability of various end points did not correlate with sensitivity to toxicants. This underscores the need for behavioral data to supplement theoretical considerations in test selection. The system's advantages are economy, high data capacity, humaneness, accessible and well-known end points, widely available equipment, automation, and the potential for direct comparisons of several different animal species.