Invited Symposium: What Can Genetic Models Tell Us About Attention-Deficit Hyperactivity Disorder (ADHD)?
Discussion and Conclusion
Conclusions on the validity of the SHR as an animal model of AD/HD
It seems that the SHR mimics the fundamentals of the behavioral characteristics of AD/HD (face validity), appears to conform with a theoretical rationale for AD/HD both in terms of hypofunctioning dopamine systems and a shorter delay-of-reinforcement gradient (construct validity), and is able to predict aspects of AD/HD behavior previously unknown (predictive validity). However, it is no reason to believe that the SHR is the only animal model that can provide valuable information as an animal model of AD/HD.
The reason why Edith Hendley developed a hyperactive but not hypertensive strain (WK-HA) and a hypertensive, but not hyperactive strain (WK-HT) by crossbreeding of SHR with WKY, followed by selected inbreeding of the desired traits  was to separate hyperactivity and hypertension. However, it is recently shown that dopamine is a major neuromodulator in the control of cortical blood flow/microcirculation as dopamine release causes local vasoconstriction . Thus, it may be that altered dopamine functions cause changes in local cerebral circulation as well as in behavior. In fact, hypertension in men and women with a family history of hypertension is associated with poorer attention and short-term memory suggesting once more a genetic link between hypertension and to impaired cognitive abilities .
A role for dopamine and other monoamine dysfunctions in AD/HD has been suspected ever since Michel LeMoal in 1969 showed that dopamine depletion following ventral-tegmental-area lesions  and Bennett Shaywitz later showed that massive dopamine depletion by the neurotoxin 6-OHDA in juvenile rats produce hyperactivity that is reversible by amphetamine [10; 11].
In comprehensive, long-term studies of neural systems underlying arousal and attention, Trevor Robbins, Barry Everitt and coworkers  have tested rats with selective neurochemical manipulations behaviorally using an analog of an attentional task developed for human subjects. They suggest that the nigrostriatal and meso-limbic dopaminergic systems are involved in response speed and vigor, the coeruleo-cortical noradrenergic system in divided and selective attention, the basal forebrain cholinergic system in stimulus detection, and the mesencephalic serotoninergic systems in response inhibition. In general terms, the SHR model of AD/HD may be subsumed in this wider theory of arousal and attention putting the major focus on the dopaminergic systems. However, all these systems are closely linked and an imbalance in one will inevitably affect the other.
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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|
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