title: Murine model of repeated exposures to conspecific trained aggressors simulates features of post-traumatic stress disorder.
abstract: 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 "cage-within-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. Behaviors affected by aggressor exposure were evaluated in a partition test wherein the subject mouse is separated from the aggressor by a fenestrated partition that permits sensory cues to pass but prevents direct physical interaction. For up to 4-6 weeks after the last aggressor exposure, subjects showed prolonged grooming, freezing, retarded locomotion and no tail rattling. PTSD and its co-morbidities are often consequent to repeated aggravated "social" assaults (e.g., combat) and manifest socially over time, suggesting the relevance of this repeated aggressor-exposure model to clinical aspects of PTSD.
authors: US Army Center for Environmental Health Research, Fort Detrick, MD 21702, USA. Rasha.Hammamieh1@us.army.mil
authors: Rasha
authors: R
authors: Hammamieh
authors: Nabarun
authors: N
authors: Chakraborty
authors: Thereza C M
authors: TC
authors: De Lima
authors: James
authors: J
authors: Meyerhoff
authors: Aarti
authors: A
authors: Gautam
authors: Seid
authors: S
authors: Muhie
authors: Peter
authors: P
authors: D'Arpa
authors: Lucille
authors: L
authors: Lumley
authors: Erica
authors: E
authors: Carroll
authors: Marti
authors: M
authors: Jett
mesh_terms: D000374:Aggression / Q000523:psychology*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001831:Body Temperature / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D002452:Cell Count / Q000379:methods; D049229:Dendritic Spines / Q000648:ultrastructure; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000473:pathology; D017397:Prefrontal Cortex / Q000166:cytology; D013154:Spleen / Q000166:cytology; D013313:Stress Disorders, Post-Traumatic / Q000503:physiopathology* / Q000523:psychology*; D013731:Territoriality