Neurobehavioral analysis methods for adverse outcome pathway (AOP) models and risk assessment

Abstract

The emerging use of neurobehavioral analysis techniques in toxicology promotes the implementation of neurobehavior, a powerful integrator of molecular, physiological, and environmental stimuli, in the development of Adverse Outcome Pathway (AOP) models. In recent years, zebrafish have been extensively investigated for their potential as a model organism in behavioral toxicology due to their low maintenance cost and similarities with rodent behavior and physiology. This chapter will review: (1) the beneficial role of neurobehavioral assays in the development of AOPs; (2) the diverse neurobehavioral endpoints to be considered in the evaluation of neurotoxicity and, (3) the challenges of integrating neurobehavioral outcomes into AOP development. Discussion of the many neurobehavioral screening assays that have been adapted from rodents to zebrafish is included. Furthermore, this chapter will review studies in which behavioral phenotypes and neurophysiological outcomes have been anchored to specific molecular initiating events induced by a chemical exposure. Although the study of the genetic and physiological basis of behavior is still nascent, there are many noteworthy studies that have enabled the creation of AOP models for the prediction of how chemical exposure affects the behavior of individuals in a population and, in turn, how these alterations can affect population dynamics.