WKHA rats with genetic hyperactivity and hyperreactivity to stress: a review

WKHA rats are a homozygous strain of hyperactive rats developed by successive selected inbreedings, starting from a cross of spontaneously hypertensive (SHR) rats with their normotensive control strain, WKY. WKHA express hyperactivity in a novel environment, as do SHRs, however their blood pressure is normotensive, thus they are potentially a more promising model of hyperactivity than the SHR. WKHA became homozygous in 1990 (20 strict brother/sister inbreedings), and they are currently in the F36 generation. Studies in collaboration with numerous colleagues have allowed us to describe a limited behavioral and neurochemical profile of WKHA rats. Their most prominent behaviors include hyperactivity in a novel environment, and a marked hyperreactivity to stress, both of which are also characteristic of SHRs. They differ from SHRs in other respects: WKHA are less aggressive, habituate more readily to a novel environment, and are less exploratory in a familiar environment than the SHR. Neurochemical studies have revealed changes in brain monoamine function in WKHA rats, particularly in frontal cortical norepinephrine and dopamine uptake, and they show marked changes in neuroendocrine responses in the hypothalamic/pituitary/adrenal axis, as well as altered POMC peptides in the pituitary anterior and posterior lobes. Molecular genetic studies by colleagues in Bordeaux have identified a quantitative trait locus for the hyperactivity/hyperreactivity trait of WKHA rats.