Murine Model of Repeated Exposures to Conspecific Trained Aggressors Simulates Features of Post-Traumatic Stress Disorder.

摘要

We evaluated repeated exposures of mice to a trained aggressor mouse as a model (adapted from social stress models of traumatic stress) for aspects of post-traumatic stress disorder (PTSD). Using a cagewithin- cage resident- intruder protocol, subject C57BL/6J mice were exposed to aggressors for 6 h daily for 5 or 10 days. At one to three random times during each 6-h session, subjects were exposed directly to aggressor for 1 min or 10 bites, whichever came first. Behavioral, physiological, and histological changes associated with aggressor-exposure were assessed for up to 6 weeks. During aggressor exposure, subjects displayed less territorial behavior, gained weight, and increased body temperature. One day after the last aggressor exposure, inflammatory cardiac histopathologies were prevalent; after 10 days, only mild myocardial degeneration with fibrosis or fibroplasias was evident, while controls showed almost no cardiac abnormalities at any time. After 4 weeks, the medial prefrontal cortex of control mice showed increased dendritic spine density, but aggressor-exposed mice showed no increase.