A MAJOR QUANTITATIVE TRAIT LOCUS INFLUENCES HYPERACTIVITY IN THE WKHARAT

The syndrome of hyperactivity describes behavioural disorders existing mainly in children and characterized by increased levels of motor act ivity, inattention and impulsivity(1,2). Overall the aetiology is poor ly understood due to the heterogeneity of the pathology although psych ological, biological and social factors acting singly or in concert ar e generally thought to be involved. In animal studies the observed hyp eractivity phenotype results from relative participation of exploratio n, 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 h yperactivity. Evidence of a genetic contribution comes from family(7,8 ) and twin studies(9) but also from the ability to select divergent an imal lines on the basis of their differential activity. The Wistar-Kyo to (WKY) and Wistar-Kyoto hyperactive (WKHA) rats are such strains - d istinct for their low and high activity scores in a novel environment, respectively(10). Here, we report the detection of a major hyperactiv ity-related QTL on chromosome 8, explaining 29% of the variance of an intercross between these strains. This study represents the first beha vioural QTL analysis in rat and provides a new starting point for biol ogically categorizing different forms of hyperactivity.