Showing that an animal is hyperactive is not sufficient for it to be accepted as a model of ADHD. Based on behavioral, genetic, and neurobiological data, the spontaneously hypertensive rat (SHR) obtained from Charles River, Germany, (SHR/NCrl) is at present the best-validated animal model of ADHD. One Wistar Kyoto substrain (WKY/NHsd), obtained from Harlan, UK, is its most appropriate control. Another WKY substrain (WKY/NCrl) obtained from Charles River, Germany, is inattentive, has distinctly different genetics and neurobiology, and provides a promising model for the predominantly inattentive subtype of ADHD (ADHD-I) if one wants to investigate categorical ADHD subtypes. In this case, also, the WKY/NHsd substrain should be used as control. Although other rat strains may behave like WKY/NHsd rats, neurobiological results indicate significant differences when compared to the WKY/NHsd substrain, making them less suitable as controls for the SHR/NCrl. Thus, there are no obvious behavioral differences among the various SHRs, but there are behavioral and neurobiological differences among the WKY strains. The use of WKY/NCrl, outbred Wistar, Sprague Dawley, or other rat strains as controls for SHR/NCrl may produce spurious neurobiological effects and erroneous conclusions. Finally, model data yield support to independent hyperactivity and inattention dimensions in ADHD behavior.
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