The Effects of Adolescent Chronic Mild Stress: In Female Wistar-Kyoto Rats

Abstract

Despite years of research to understand under-lying mechanisms and develop more effective treatment approaches for mood disorders, numerous challenges exist. Many chronic stress models are used to study mood disorders, how-ever the majority have been established with adult males. This is problematic considering that affective disorders are more common in women, and generally develop during late adolescence. Studies have indicated fundamental behavioral, physiological, and neural differences between males and females in response to the same external stressors, furthering a need to develop sex-specific paradigms to accurately model the etiology of mood disorders in females. The Wistar-Kyoto (WKY) rat strain is a promising model known to demonstrate endogenous hormonal and behavioral abnormalities similar to symptom-presenting patients with depression. In this study, we test stress susceptibility of female WKY rats by using a three-week chronic mild stress (CMS) paradigm during late adolescence. We hypothesize that female WKY rats undergoing CMS will develop depressive-and anxiety-like characteristics that are typically not observed in a Wistar strain. Body weight, food intake, body composition, and corticosterone levels throughout CMS are determined to evaluate physiological effects of stress. Immediately following CMS, animals undergo behavioral assessments of helplessness, anxiety, anhedonia, and locomotor activity to evaluate the development of mood disorder phenotypes. These tests are repeated during late adulthood to determine whether expected stress-induced behavioral deficits persist later in life. The validation and characterization of this sex-specific model of mood disorders allows for more studies on the underlying mechanisms driving these disorders and ultimately contribute to the development of novel therapeutic strategies.