title: New dimensions in the use of rodent behavioral tests for novel drug discovery and development.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: a Centro de Investigación en Reproducción Animal (CIRA) , Universidad Autónoma de Tlaxcala-CINVESTAV , Tlaxcala , Mexico.
authors.forename: Kurt L
authors.initials: KL
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D001008:Anxiety Disorders / Q000188:drug therapy / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects*; D003863:Depression / Q000188:drug therapy / Q000503:physiopathology; D004195:Disease Models, Animal; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy* / Q000503:physiopathology; D012377:Rodentia
keywords: Anhedonia; CO2 sensitivity; animal model; anxiety; behavioral inhibition; depression; endophenotype; fear generalization; internalizing; mouse; rat; startle reflex