Nonhuman Primates in Neurotoxicity Screening and Neurobehavioral Toxicity Studies

Abstract

Nonhuman primates can be used to develop models that use complex behaviors to evaluate the toxicity of pharmaceutical and other products, Primate functional observational batteries (FOBs) can be designed to resemble those used in rodent tests, although they need not focus on simple conditioned motor responses as small mammal FOBs frequently do. Primates generally are not suitable for use in most (first-tier) neurotoxic screening tests for both practical and scientific reasons, as well as for ethical ones. With regard to practicality factors of cost, animal availability, husbandry, and housing, and observer labor intensity, all increase with the use of primates. With regard to research design, accumulating evidence indicates that primate pharmacologic responsivity is affected by social variables in such a way that group-housed animals provide more realistic (valid) models of human neurobehavioral and disease processes in general. This further complicates primate use and behavioral measurement and evaluation. Data from a long-term study of semipermanant behavioral and electrophysiologic alterations brought about by extended exposure to a psychoactive medication are presented in order to illustrate these points and to indicate how such measures can be useful, and at times indispensable, in second-tier evaluation.