New dimensions in the use of rodent behavioral tests for novel drug discovery and development

ABSTRACT

Introduction: Dimensional models of psychopathology describe mental illness in terms of natural variance along certain phenotypic dimensions that are continuous with normal. Vulnerability to psychopathology might arise when certain adaptive psychophysiological processes, conserved between humans and non-human animals, function outside of their “normal” range. Therefore, an in-depth understanding of the neurobiology and neurochemistry underlying these processes could identify possible novel drug targets.

Areas covered: Psychophysiological processes that might be related to anxiety disorders and depression are proposed and discussed. Those processes relevant to depressive disorders include: hedonic responsiveness, biases in the processing of stimuli, and sleep architecture. Those relevant to anxiety disorders include: startle reactivity, CO₂ sensitivity, and fear generalization. Rodent behavioral tests for assessing the function of these processes and investigating their neurobiology are described. A psychophysiological process strategy for translational research is proposed, which focusses on understanding the neurobiology and neurochemistry underlying key psychophysiological processes that, when their activity deviates from normal, are associated with neuropsychiatric symptoms. This strategy emphasizes the use of analogous tests and measures in both preclinical and clinical studies, while de-emphasizing the use of preclinical animal models that attempt to replicate features of the neuropsychiatric disorder through experimental manipulations.

Expert opinion: Investigating the neurobiology of key psychophysiological processes in rodents should enhance our understanding of the pathophysiology of neuropsychiatric disorders. New drug development could be directed toward developing pharmacological strategies that would normalize the function of these psychophysiological processes.