Invited Symposium: What Can Genetic Models Tell Us About Attention-Deficit Hyperactivity Disorder (ADHD)?



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A Behavioral Validation of the Spontaneously Hypertensive Rat (SHR) as an Animal Model of Attention-Deficit/Hyperactivity Disorder (AD/HD)

Contact Person: Terje Sagvolden (terje.sagvolden@basalmed.uio.no)


In the literature on animal models of Attention-Deficit/Hyperactivity Disorder (AD/HD) there has not yet been any systematic discussion on how to decide the validity of these models. Since there is no biological marker identified and diagnosing AD/HD is based on behavioral symptoms, it might be fair to claim that "the core symptoms of disorder ... need to be understood before one can be clear about what neuropsychological processes are relevant, or what would be an adequate animal model" ([1], p. 12).

Inattentiveness, overactivity and impulsiveness are presently regarded as the main clinical symptoms of AD/HD. Although, there is considerable overlap between these symptoms, impulsiveness is increasingly seen as the symptom of greatest significance [1].

Animal Models of AD/HD

In all areas of research one is trying to find or build models that can be used to summarize and simplify the understanding of a disorder, research problem or phenomenon under investigation. In clinical research there are several advantages associated with animal models of disorders . The researcher deals with a simpler system yielding data that may be easier to interpret than the full-blown clinical case, the groups may be genetically more homogeneous, environmental control is simpler, interventions of various sorts are possible, etc.

There is a plethora of animal models of AD/HD: rats selected from a general population [2], rats reared in social isolation [3], rats exposed to environmental pollutants (lead: [4], polychlorinated biphenyls (PCBs): [5; 6]); rats that have undergone neonatal anoxia [7]: rats that have undergone hippocampal X-irradiation in infancy [8]; rats that have undergone neurotoxic brain lesions [9-11], genetic models (SHR: [12-23]; Naples High/Low Excitability Rats: [24; 25]; knock out mice [26].

The SHR is the most-frequently-used AD/HD model. This is a strain that has been bred from progenitor Wistar Kyoto rats (WKY, [27]). By crossbreeding of SHR with WKY, followed by selected inbreeding of the desired traits, Edith Hendley [28; 29] developed the SHR and WKY strains further into a hyperactive but not hypertensive strain (WK-HA) and a hypertensive, but not hyperactive strain (WK-HT).

The SHR is hyperactive in a variety of behavioral paradigms [14; 15; 17-19; 21-23]. SHR, WK-HA and WK-HT hyperactivity in activity tests depends on the parameters of the test situation (free- vs. forced open fields, duration of testing, illumination of the field etc.) [19; 21; 28]. All three strains develop hyperactivity in free-exploration open fields [19].

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Sagvolden, T.; (1998). A Behavioral Validation of the Spontaneously Hypertensive Rat (SHR) as an Animal Model of Attention-Deficit/Hyperactivity Disorder (AD/HD). Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/sadile/sagvolden0567/index.html
© 1998 Author(s) Hold Copyright