Elsevier

Biological Psychiatry

Volume 57, Issue 11, 1 June 2005, Pages 1239-1247
Biological Psychiatry

Advancing the neuroscience of ADHD
Rodent Models of Attention-Deficit/Hyperactivity Disorder

https://doi.org/10.1016/j.biopsych.2005.02.002Get rights and content

An ideal animal model should be similar to the disorder it models in terms of etiology, biochemistry, symptomatology, and treatment. Animal models provide several advantages over clinical research: simpler nervous systems, easily interpreted behaviors, genetic homogeneity, easily controlled environment, and a greater variety of interventions. Attention-deficit/hyperactivity disorder (ADHD) is a neurobehavioral disorder of childhood onset that is characterized by inattentiveness, hyperactivity, and impulsiveness. Its diagnosis is behaviorally based; therefore, the validation of an ADHD model must be based in behavior. An ADHD model must mimic the fundamental behavioral characteristics of ADHD (face validity), conform to a theoretical rationale for ADHD (construct validity), and predict aspects of ADHD behavior, genetics, and neurobiology previously uncharted in clinical settings (predictive validity). Spontaneously hypertensive rats (SHR) fulfill many of the validation criteria and compare well with clinical cases of ADHD. Poor performers in the five-choice serial reaction time task and Naples high-excitability rats (NHE) are useful models for attention-deficit disorder. Other animal models either focus on the less important symptom of hyperactivity and might be of limited value in ADHD research or are produced in ways that would not lead to a clinical diagnosis of ADHD in humans, even if ADHD-like behavior is displayed.

Section snippets

Advantages of Animal Models

Optimal animal models should be similar to clinical cases in terms of etiology, biochemistry, symptomatology, and treatment (McKinney and Bunney 1969). Models usually have simpler nervous systems, and their behaviors are easier to interpret than clinical cases. Additionally, models are often more genetically homogeneous, their environment is easy to control, and more interventions are possible than in clinical cases.

General Validation Criteria for Animal Models

Sarter et al (1992) developed validation criteria for animal models of human disorders. Recently, criteria for assessing models for ADD and ADHD were proposed (Sagvolden 2000). An ADHD model must conform to three validation criteria: face validity, construct validity, and predictive validity. Face validity is the ability to fundamentally mimic the behavioral clinical characteristics of the disorder. Construct validity conforms to a theoretical rationale for the disorder. Predictive validity is

Criteria for Face Validity

Children with ADHD and control subjects react differently to reinforcers. The major behavioral characteristics of children with ADHD can be demonstrated with multiple fixed-interval/extinction schedules of reinforcement (FI/Ext schedules) with two or more components that operate in alternation, each in the presence of a different stimulus (Sagvolden et al 1998). The fixed-interval component delivers reinforcers at fixed time intervals when the required response is performed (e.g., a lever is

Spontaneously Hypertensive Rat

The spontaneously hypertensive rat (SHR) is the most frequently used model of ADHD (Sagvolden 2000). It is a genetic model bred from progenitor Wistar Kyoto rats (WKY) (Okamoto and Aoki 1963).

Conclusions

Strict criteria have introduced objectivity to the study of animal models of ADD and ADHD; however, it is impossible to completely fulfill the requirements for assessing the validity of animal models because of the inadequate understanding of ADHD.

Of all the animal models that have been proposed, the SHR best fits the criteria for ADHD, whereas NHE rat and poor 5-CSRT performers promise to be useful models for ADD. Other animal models either focus on the less important symptom of hyperactivity

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