Comparisons of behavioral and neurochemical characteristics between WKY, WKHA, and Wistar rat strains.

WKHA rats constitute a recombinant inbred rat strain derived by phenotypic selection of the progeny of hybrid F2 crosses between SHR and WKY rats. WKHA are normotensive and show some features of hyperactivity and of hyper-reactivity to stress, but their utility as model of attention deficit/hyperactivity disorder (ADHD) has not yet been settled. To address these questions, we performed behavioral and neurochemical evaluations of WKHA, and compared them to both WKY and Wistar (WIS) rats. In locomotor activity tests, the respective scores for each strain were WKY<WKHA<WIS. The relative amplitudes of the inhibition of the startle response by preexposure of the animals to a low-level acoustic cue (prepulse inhibition (PPI) stimulus filtering test) were WKY< WKHA = WIS. In nontreated rats, prepulse inhibition was significantly lower in WKY than in WIS and WKHA rats at low prepulse intensity. Methylphenidate did not decrease locomotor activity in any of the strains, but rather increased locomotion, with the effect being of higher amplitude in WKY. Methylphenidate also impaired prepulse inhibition in a dose-dependent manner. In situ hybridization for NGFI-B, a transcription factor related to the dopaminergic system, revealed that methylphenidate increased the expression of NGFI-B mRNA in the accumbens (core/shell) and striatum only in WKY rats. We conclude that: (1) the behavioral differences between WKY and WKHA can be more readily explained by deficits present in WKY than by unusual characteristics of WKHA, (2) the WKHA does not appear to represent a useful model of ADHD, and (3) the use of WKY rats as the only control for behavioral studies is potentially misleading, because they show a combination of behavioral and neurochemical (dopamine-related) characteristics that make them very different from other common rat strains. Although these characteristics may make them interesting models in their own right, it also follows that the conclusions of any study based on comparisons of one particular strain to just WKY should be interpreted very cautiously.