A major quantitative trait locus influences hyperactivity in the WKHA rat

The syndrome of hyperactivity describes behavioural disorders existing mainly in children and characterized by increased levels of motor activity, inattention and impulsivity(1,2). Overall the aetiology is poorly understood due to the heterogeneity of the pathology although psychological, biological and social factors acting singly or in concert are generally thought to be involved. In animal studies the observed hyperactivity phenotype results from relative participation of exploration, emotionality and general activity(3). Studies using brain lesions(3), neuropharmacology(4) and gene knock-out strategies(5,6) have shown that specific elements of the brain dopaminergic system can subserve hyperactivity. Evidence of a genetic contribution comes from family(7,8) and twin studies(9) but also from the ability to select divergent animal lines on the basis of their differential activity. The Wistar-Kyoto (WKY) and Wistar-Kyoto hyperactive (WKHA) rats are such strains - distinct for their low and high activity scores in a novel environment, respectively(10). Here, we report the detection of a major hyperactivity-related QTL on chromosome 8, explaining 29% of the variance of an intercross between these strains. This study represents the first behavioural QTL analysis in rat and provides a new starting point for biologically categorizing different forms of hyperactivity.