Using identical behavioral tasks in children, monkeys, and rats to study the effects of drugs

Abstract

Background: The need to use animal models to predict the effects of drugs on the nervous system has led to the development of automated systems for the assessment of specific behaviors—identical in both humans and laboratory animals—that represent aspects of specific cognitive processes. At the National Center for Toxicological Research (NCTR), a battery of operant behavioral tasks (the NCTR Operant Test Battery, or OTB) has been developed to model specific behaviors associated with motivation, color and position discrimination, time estimation, short-term memory and attention, and learning. Objectives: The goals of this paper were to describe interspecies similarities in specific behaviors designed to model a variety of cognitive functions and to argue for the use of such behaviors in risk assessments (preclinical studies), monitoring treatment efficacy, and postmarket surveillance. Methods: The literature search was primarily limited to automated systems that are useful in rodents, monkeys, and children. Results: Maintenance of task continuity across species allows for the determination of interspecies similarities in brain function and aids in the extrapolation of data from animals to humans. Comparative data indicate, for example, that the OTB performance of well-trained monkeys is generally indistinguishable from that of children. The demonstration that human OTB performance correlates significantly with intelligence (IQ scores) highlights the relevance of these measures. Results of comparative drug studies indicate that monkeys are good predictors of drug effects in humans. Recent studies have shown that rodent performance in some of these complex tasks is also similar to that of monkeys and children, and that for some drugs, responses are similar to those for monkeys and, presumably, humans. Conclusions: Tools such as the NCTR OTB may provide the opportunity for extensive interspecies comparisons of cognitive processes and provide the means for studying the effects of psychoactive agents by use of relevant end points in a variety of animal models. Such approaches may provide laboratory animal data that could predict adverse drug events in humans, as defined by disturbances in aspects of complex brain function. Likewise, use of similar instruments in the clinic, even in the pediatric setting, could provide longitudinal data—in the same patients—on treatment efficacy and toxicity during clinical trials and postmarket surveillance.