Changes in behavior and ultrasonic vocalizations during antidepressant treatment in the maternally separated Wistar-Kyoto rat model of depression.

Genetic predisposition and stress are major factors in depression. The objective of this study was to establish a robust animal model of depression by selecting the appropriate substrain of the Wistar-Kyoto (WKY) rat, and subjecting these rats to the stress of maternal separation during the early stages of development. The initial experiment identified WKY/NCrl as the appropriate substrain of WKY to use for the study. In the second part of the study, depression-like behavior and ultrasonic vocalizations (USVs) were recorded in WKY/NCrl and maternally separated WKY/NCrl rats during the course of reversal of depression-like behavior. Wistar rats served as the reference strain. In adulthood, non-separated WKY/NCrl, maternally separated WKY/NCrl and Wistar rats were injected intraperitoneally with either saline or desipramine (15 mg/kg/day) for 15 days and their behavior recorded. Desipramine decreased immobility and increased active swimming and struggling behavior of WKY/NCrl in the FST and also decreased their USVs in response to removal of cage mates. The USVs in this study appeared to signal an attempt to re-establish social contact with cage mates and provided a measure of social dependence. Maternally separated WKY/NCrl rats displayed more anxiety than normally reared WKY/NCrl rats and responded to the anxiolytic effects of desipramine. The present findings support the use of WKY/NCrl as an animal model of depression. Maternal separation increased the anxiety-like behavior of the WKY/NCrl, thus providing a robust model to study depression- and anxiety-related behavior.