The relevance of animal models for neurotoxic disease states

This paper has dealt with the use of animal models of neurotoxic disease for developing and validating markers of exposure and effect. In most of the examples cited, the animal models resembled human disease states in terms of exposure rather than effect. As indicated above, it is generally unlikely that experimental models, using similar exposures and even involving similar sites and extent of toxic action, will result in neurobehavioral effects that resemble human neuropsychiatric disease states. The search for homology of expression can, in most instances, be misleading and involve somewhat tortuous claims of similarity. Until there is good agreement on the relationship between certain well-described human mental ilnesses and behavioral states in aminals, this will not yield much helpful information. In the absence of such agreement, certain fundamental behavioral states in animals, such as locomotor activity, active and passive avoidance, and simple maze learning, are likely to be most useful for determining neurotoxic effects. Attempts to describe spontaneously elicited behaviors in rodents more comprehensively and quantitatively have been made on only a limited basis; better description of standard behaviors - e.g., exploration, catelepsy, and gait - can be developed to yield more information. These approaches have already demonstrated sensitivity for detecting early neurotoxic effects, as in our studies of the effects of estradiol and the artificial food color erythrosin B on response to cateleptogenic agents. In preparation and the effects of manganese and kainic acid on gait and locomotion. Finally, there is a need to increase communication between clinical and experimental toxicologists, so that clinical researchers can extract from the experimental literature the findings that are applicable as markers of exposure and effect, and experimental researchers can undertake studies that will provide information from animals that can also be explored in humans.