Psychosocial animal model of PTSD produces a long-lasting traumatic memory, an increase in general anxiety and PTSD-like glucocorticoid abnormalities Phillip R. Zoladz a , Monika Fleshner b , David M. Diamond c,d, * a Department of Psychology & Sociology, Ohio Northern University, Ada, OH, USA b Department of Integrative Physiology & Center for Neuroscience, University of Colorado, Boulder, CO, USA c Research and Development Service, VA Hospital, Tampa, FL, USA d Departments of Psychology and Molecular Pharmacology & Physiology, Center for Preclinical & Clinical Research on PTSD, University of South Florida, Tampa, FL, USA Received 10 August 2011; received in revised form 3 February 2012; accepted 14 February 2012 1. Introduction Individuals exposed to intense, life-threatening trauma are at significant risk for developing post-traumatic stress dis- order (PTSD). People who develop PTSD respond to a trau- matic experience with intense fear, helplessness and horror Psychoneuroendocrinology (2012) 37, 1531—1545 KEYWORDS Stress; Trauma; Glucocorticoids; HPA axis; Memory; Dexamethasone; Animal model; Fear conditioning Summary Post-traumatic stress disorder (PTSD) is characterized by a pathologically intense memory for a traumatic experience, persistent anxiety and physiological abnormalities, such as low baseline glucocorticoid levels and increased sensitivity to dexamethasone. We have addressed the hypothesis that rats subjected to chronic psychosocial stress would exhibit PTSD-like sequelae, including traumatic memory expression, increased anxiety and abnormal glucocorticoid responses. Adult male Sprague-Dawley rats were exposed to a cat on two occasions separated by 10 days, in conjunction with chronic social instability. Three weeks after the second cat exposure, the rats were tested for glucocorticoid abnormalities, general anxiety and their fear-conditioned memory of the two cat exposures. Stressed rats exhibited reduced basal glucocorticoid levels, increased glucocorticoid suppression following dexamethasone adminis- tration, heightened anxiety and a robust fear memory in response to cues that were paired with the two cat exposures. The commonalities in endocrine and behavioral measures between psychosocially stressed rats and traumatized people with PTSD provide the opportunity to explore mechanisms underlying psychological trauma-induced changes in neuroendocrine sys- tems and cognition. # 2012 Elsevier Ltd. All rights reserved. * Corresponding author at: Department of Psychology, 4202 E. Fowler Ave. (PCD 4118G), University of South Florida, Tampa, FL 33620, USA. Tel.: +1 813 974 0480; fax: +1 813 974 4617. E-mail address: ddiamond@usf.edu (D.M. Diamond). Available online at www.sciencedirect.com j our na l h omepa g e: www.e lse vie r.c om/l oca te/ psyne ue n 0306-4530/$ — see front matter # 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.psyneuen.2012.02.007