The Wistar-Kyoto rat as a model relevant to inattentive ADHD: substrain variability and affective comorbidity

Wistar-Kyoto (WKY) rats, originally used as a control group for spontaneously hypertensive rats, are increasingly recognized as a valuable model for studying selected neuropsychiatric disorders. This strain exhibits behavioral and neurobiological traits relevant to both depression and inattentive attention-deficit/hyperactivity disorder (ADHD), including behavioral inhibition, increased stress sensitivity, anhedonic behaviors, and deficits in sustained attention. At the same time, a significant challenge remains in the form of considerable variability among WKY substrains, resulting from genetic differences and the breeding practices employed by individual suppliers. This variability may limit the reproducibility of results, but it also holds research value, enabling the analysis of distinct dimensions of mental disorders within related animal models. The aim of this review is to integrate available data on the genealogy, genetic variability, and behavioral phenotypes of WKY rats, with particular emphasis on their relevance to ADHD research and on depression-related traits that may influence the interpretation of WKY rats as a reference or disease-relevant strain. The added value of the present review is therefore to provide an integrated ADHD-oriented perspective on the WKY strain, while also considering depression-related and treatment-response traits as biologically relevant components of its complex behavioral phenotype.