Behavioral indices of neurotoxicity: what can be measured?

The ability to identify and characterize the potential neurotoxicity of chemicals is an important and necessary function of various regulatory agencies. Behavioral assessments of toxicity may be important because of their relative sensitivity to some chemicals, their generally noninvasive characteristics, and their ability to measure toxicity in organ systems other than the nervous system. Behavioral tests can be classified by several criteria including traditional experimental definitions, their desired experimental usage, the neurobehavioral functions they are designed to assess, and the strategy chosen for their use in the evaluation of chemicals. Examples of neurobehavioral tests used to evaluate the effects of chemicals for toxicity include those that evaluate motor (spontaneous motor activity, motor coordination, weakness, abnormal movement or posture, tremor, and on-going performance), sensory (screening, reflex modification, and instrumental conditioning), learning/memory (nonassociative and associative), instrumental performance (schedules of reinforcement), and naturally occurring responses (consummatory behaviors). Behavioral procedures have also been utilized in select ways in toxicological research to detect latent damage, to study mechanisms of action, and to screen for functional dysfunction following exposure during development. Many considerations, such as the behavioral mechanism of action, definition of an adverse effect, problem of functional reserve, and several statistical questions, should be taken into account in the use and interpretation of data obtained from behavioral tests. During the last decade, there have been numerous recommendations from groups within the United States and, most recently, the World Health Organization, suggesting that systematic observational assessments may be appropriate when carried out within already existing toxicological protocols.