Source Paper
Evaluation of animal models of neurobehavioral disorders
F Josef van der Staay, Saskia S Arndt, Rebecca E Nordquist
Behavioral and Brain Functions • 2009
Source Paper
F Josef van der Staay, Saskia S Arndt, Rebecca E Nordquist
Behavioral and Brain Functions • 2009
Objective: This document is a methodological review paper on animal model evaluation, not a specific experimental protocol. It uses the neonatal hippocampal lesion rat model as an example to illustrate model evaluation criteria, but does not describe a complete reproducible experimental procedure with specific methods, equipment, or detailed steps.
Define the specific purpose(s) of the neonatal hippocampal lesion model before development and testing
Note: The starting point of model building is definition of purpose(s)
“The starting point of the process of model building is the definition of the purpose(s) of the model”
Develop and test the neonatal hippocampal lesion model based on defined purposes
Note: Model development requires multidisciplinary approach with preclinical and clinical experts
“Then, the model is developed and tested. Model development requires a multidisciplinary approach.”
Evaluate the model considering scientific criteria (reliability, replicability, predictive validity, construct validity, external validity) and animal welfare issues
Note: Evaluation takes into account both scientific validity and animal welfare considerations
“The evaluation of the model takes into consideration the questions it is expected to answer, its validity – in particular predictive, construct – and external validity or generalizability. Simultaneously, it takes animal welfare issues into account”
Define site and size of neuronal damage (neuropathology) and effects on specific neuronal circuits or neurotransmitter systems
Note: Neuropathological changes are dependent variables in the model
“Damage or dysfunctions induced: site and size of neuronal damage (neuropathology), effects on specific neuronal circuits or neurotransmitter systems”
Define behavioral dysfunctions including impaired cognitive performance, impaired sensorimotor functions, and neuropsychiatric symptoms as dependent variables
Note: Behavioral changes are dependent variables measured in the model
“Behavioral dysfunction or malfunction: impaired cognitive performance, impaired sensorimotor functions, neuropsychiatric symptoms, behavioral (endo)phenotypes”
Evaluate how consistent assessment/testing methods are and the degree of accordance between results of the same experiment performed independently
Note: Apply multiple-tiered replication battery to estimate reliability, validity, and generalizability
“One may apply a multiple-tiered 'replication battery' to estimate the reliability/replicability, validity, and generalizability of result”
Evaluate the degree of descriptive similarity between behavioral dysfunction in the animal model and in humans with the neurobehavioral disorder
Note: Face validity is similarity of symptoms between model and human condition
“Face validity is the degree of descriptive similarity between, for example, the behavioral dysfunction seen in an animal model and in the human affected by a particular neurobehavioral disorder”
Evaluate whether the model measures the theoretical constructs it is intended to measure regarding brain-behavior relationships
Note: Construct validity is a major criterion for model evaluation
“Validity in that sense is a major criterion for evaluating animal models”
Evaluate whether findings from the animal model can predict outcomes in humans or other species
Note: Predictive validity is essential for translating findings to clinical applications
“The evaluation of the model takes into consideration the questions it is expected to answer, its validity – in particular predictive, construct”
Evaluate whether results can be generalized beyond the laboratory setting to other conditions and populations
Note: External validity must be verified after internal validity is established
“It does not make sense to speculate about the external validity/generalizability of experimental studies outside the laboratory, in the 'Outside World' or 'Real World', as long as it has not been verified that the results are valid within the laboratory”
Assess whether animal welfare is compromised and determine if action is needed to reduce discomfort
Note: Compromised welfare is inherent in many deficiency models; discontinue if welfare severely compromised
“Weighing the animal's welfare and considerations as to whether action is indicated to reduce the discomfort must accompany the scientific evaluation at any stage of the model building and evaluation process”
Determine whether to continue model development based on whether preset scientific criteria are met and animal welfare is acceptable
Note: Discontinue model building if criteria not met or welfare severely compromised
“Animal model building should be discontinued if the model does not meet the preset scientific criteria, or when animal welfare is severely compromised”
Model used to study schizophrenia-related behavioral and neuropathological changes