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Table 1 Overview of animal models.

From: Evaluation of animal models of neurobehavioral disorders

A: Types of 'model animals'
Normal animals Animals with naturally occurring deficits Animals with experimentally induced deficits
Normal subjects, i.e. animals without any observable behavioral deficit Note: At first glance, normal animals are not model animals for the study of neurobehavioral disorders. However, they may be used for drug screening, or as in vivo (behavioral) bioassay. Normal animals are used to • assess the safety/toxicology risk of a putative therapeutic; • obtain an estimate of the putative abuse liability of a compound; • explore the neurobiological specificity of compounds and their molecular and cellular mechanisms of action In addition: studying behavior in normal animals provides the baseline data for identifying abnormal behavior Spontaneously and endogenously occurring psychiatric or neurological conditions; spontaneously occurring mutations; aging animals Genetic lines: inbred strains and their crossings Selection lines, established through artificial selection favoring low and/or high values of a particular trait within a given population for a number a successive generations; preferentially including an unselected control line for comparison Selected extremes from a particular animal population, e.g. good vs. poor learners, dominant vs. subordinate animals, non-aggressive vs. aggressive animals Transgenic and knockout animals; Chromosomal substitution strains; animals from mutagenesis screens (after thorough phenotyping and validation) Selection lines resulting from selective breeding Environmental factors: e.g. animals experiencing acute or chronic stress, pain, or sleep deprivation Animals with disruptions induced by dietary composition (e.g. tryptophan depletion), pharmacological compounds (e.g. scopolamine, MK-801), or electrically, or by hypoxia or anoxia Animals with focal or global ischemic, embolic, or hemorrhagic cerebral stroke Animals with CNS-specific lesions: neuro- or immunotoxic lesions; lesions induced by aspiration, ablation (knife cuts); radio-frequency lesions, cryogenic lesions
B: Independent and dependent variables
Independent variable (the model animals listed in part A) Dependent variables and/or (endo)phenotypes
  Neuropathological changes Behavioral changes
E.g. genetically modified animal, aged animal, lesioned animal, ischemic animal, hypoxic animal, aged and lesioned animal, i.e. combination of deficits (see part A) Damage or dysfunctions induced: site and size of neuronal damage (neuropathology), effects on specific neuronal circuits or neurotransmitter systems, psychophysiological and biological (endo)phenotypes Behavioral dysfunction or malfunction: impaired cognitive performance, impaired sensorimotor functions, neuropsychiatric symptoms, behavioral (endo)phenotypes
  Homology of damaged area(s) or neuropathological changes. Homology of disrupted processes or impaired functions
  Operational definition(s) of the neuropathological (endo)phenotype(s) Operational definition(s) of the behavioral (endo)phenotype(s)
C: Setting criteria for model building and model evaluation
  Experts: clinicians, pathologists, molecular biologists, etc., depending on which aspects of the animal model are considered Experts: behavioral scientists such as psychiatrist, (bio)psychologists, ethologists, behavioral pharmacologists
  Experts must: • define as exactly as possible the (neuro)pathological symptoms to be modeled; • elaborate a set of model evaluation criteria Experts must: • define the behavioral (dys)functions to be modeled as precisely as possible, possibly derived from clinical diagnostic criteria; • elaborate a set of model evaluation criteria, which may be derived from psychological test theory for the tests applied to assess the dysfunctions
  1. Part A lists different types of 'model animals' for the study of behavioral dysfunctions (modified from [33]). It focuses on the type of subject (independent variable) and is not concerned with the type of dependent variable measured
  2. In part B, (modified from [10]), the independent and the dependent variables in deficiency models are tabulated.
  3. In part C, the expertise needed to define criteria for building a 'good' animal model and for its evaluation is listed. The validity of a model should be determined using multidisciplinary, interdisciplinary, or – preferentially – transdisciplinary approaches (the latter addressing a common problem against the background of a shared conceptual framework by employing theories, concepts and scientific methods of the different disciplines involved; [34]). No explicit set of rules exists for the mental, physical, and/or neuro(patho)logical changes (2nd column) that are considered to cause the behavioral dysfunctions (3rd column).