The Wistar Kyoto rat (WKY) is a specific strain of laboratory rat widely used in scientific research. This inbred strain originated from Wistar rats at Kyoto University in 1960. It was developed by selecting Wistar rats that exhibited normal blood pressure, serving as a genetic control for the spontaneously hypertensive rat (SHR) strain. The WKY strain was brought to the National Institutes of Health (NIH) in 1971 and later distributed to other research facilities. Over the years, the WKY rat has become a recognized model for various physiological and behavioral studies.
Distinctive Traits
Wistar Kyoto rats possess distinct physiological and behavioral characteristics, making them valuable research models. While initially selected as a normotensive control for the spontaneously hypertensive rat, some WKY colonies show an incidence of spontaneous hypertension and higher blood pressure. This cardiovascular profile makes them useful for studies related to blood pressure regulation.
WKY rats are also recognized for their altered stress response, including anxiety and depression-like behaviors. They exhibit an exaggerated physiological response to stressful environments, often choosing withdrawal, avoidance, or freezing behaviors in novel situations. Their despair-like behavior and passive coping with stress highlight their relevance as a model for certain human psychiatric conditions. The genetic makeup of WKY rats and their substrains contains variations that affect genes implicated in human genetic studies of depression, supporting their use in such research.
Key Research Contributions
Wistar Kyoto rats are instrumental in advancing scientific understanding across several fields, particularly cardiovascular research, stress-related disorders, and neurobiology. In cardiovascular research, WKY rats are often compared with spontaneously hypertensive rats (SHR) to understand the genetic and physiological factors contributing to hypertension. Studies using WKY rats have helped differentiate stress-induced cardiovascular responses between hypertensive and normotensive strains, showing variations in heart rate and blood pressure changes.
For stress-related disorders, WKY rats are recognized as an animal model for depression and anxiety, exhibiting behaviors such as passive coping, despair-like states, and heightened sensitivity to stress. Researchers have gained insights into underlying mechanisms, including hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and alterations in the endocannabinoid system, both implicated in human stress responses. These rats also show cognitive impairments and can be resistant to traditional antidepressants, making them valuable for exploring novel treatment strategies for treatment-resistant depression.
Neurobiological research utilizes WKY rats due to their inherent neurobiological differences. Their responses to various stimuli, including environmental, pharmacological, and physical stressors, differ from other strains, allowing investigations into the neural circuits and molecular pathways involved in stress and mood disorders. This contributes to a deeper understanding of brain function in the context of mental health.
Care and Ethical Considerations
The use of Wistar Kyoto rats in scientific research adheres to established principles of animal care and ethical guidelines. Researchers are obligated to ensure the welfare of these laboratory animals, minimizing discomfort, distress, or pain throughout the research process. This commitment aligns with the “3Rs” principles: Replacement, Reduction, and Refinement.
Replacement involves seeking alternatives to animal use when feasible. Reduction focuses on using the fewest animals necessary to obtain statistically significant results. Refinement emphasizes improving animal welfare and minimizing suffering through optimized housing, handling, and experimental procedures. Ethical committees, such as Institutional Animal Care and Use Committees (IACUCs), review research protocols to ensure compliance with these guidelines and regulations, promoting responsible and humane treatment of Wistar Kyoto rats in scientific investigations.