Functional assays for neurotoxicity testing

Neurobehavioral and pathological evaluations of the nervous system are complementary components of basic research and toxicity testing of pharmaceutical and environmental chemicals. While neuropathological assessments provide insight as to cellular changes in neurons, behavioral and physiological methods evaluate the functional consequences of disruption of neuronal communications. The underlying causes of certain behavioral alterations may be understood, but many do not have known direct associations with specific brain pathologies. In some cases, however, rapidly expanding mouse models (transgenic, knock-out) are providing considerable information on behavioral phenotypes of altered pathology. Behavior represents the integrated sum of activities mediated by the nervous system, and functional tests used for neurotoxicity testing tap different behavioral repertoires. These tests have an advantage over pathologic measures in that they permit repeated evaluation of a single animal over time to determine the onset, progression, duration, and reversibility of a neurotoxic injury. Functional assays range from a screening-level battery of tests to refined procedures to tap specific forms of learning and/or memory. This article reviews common procedures for behavioral toxicity testing and provides examples of chemical-specific neurobehavioral-pathological correlations in order to inform interpretation and integration of neuropathological and behavioral outcomes.