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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.

journal_name

Behav Brain Res

journal_title

Behavioural brain research

authors

Hammamieh R,Chakraborty N,De Lima TC,Meyerhoff J,Gautam A,Muhie S,D'Arpa P,Lumley L,Carroll E,Jett M

doi

10.1016/j.bbr.2012.07.022

subject

Has Abstract

pub_date

2012-11-01 00:00:00

pages

55-66

issue

eissn

0166-4328

issn

1872-7549

pii

S0166-4328(12)00478-0

journal_volume

235

pub_type

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Murine model of repeated exposures to conspecific trained aggressors simulates features of post-traumatic stress disorder.