Chapter 3.1 Animal models of posttraumatic stress disorder
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Posttraumatic stress disorder (PTSD) is a potential consequence of being exposed to or witnessing an event provoking fear, helplessness, or horror. It is characterized by several debilitating symptoms including persistent hyperarousal, unwanted memories and thought intrusions, and hyperavoidance of stimuli or situations associated with the original trauma. The neurobiological mediators of these symptoms, however, still require elucidation, and animal models are particularly well suited for investigation of these mechanisms. Although the behavioral literature contains a large number of models that involve exposing animals to intense stressors, only a few of these are able to reproduce the biological and behavioral features of PTSD characteristic of a pathophysiological stress response. Among these are models involving single episodes of inescapable shock, which produce several bio-behavioral effects characteristic of PTSD, including opioid-mediated analgesia, noradrenergic sensitization as well as fear-conditioning effects. Single prolonged stress, involving the sequential exposure of rats to restraint, forced swim, and ether anesthesia, is able to produce an enhanced negative feedback of the HPA axis, as observed in PTSD patients, as well as a sustained exaggeration of the acoustic startle response. Predator exposure models, which invoke a significant threat of injury or death to particular animals, are effective in producing behavioral changes potentially analogous to hyperarousal symptoms, as well as changes in amygdala sensitization and long-term potentiation. In addition to these PTSD-specific models, several putative models, including single episodes of restraint/immobilization, forced swim, or early-life maternal separation, show promise as potential PTSD models, but require further validation and characterization before they might be considered specific to this disorder. Given the complexity of PTSD, both in terms of causal factors and symptoms, it is becoming apparent that multiple, independent physiological pathways might mediate this disorder. Future research may, therefore, wish to focus on endophenotypic models, which attend to one specific physiological pathway or neurobiological system, rather than attempt to reproduce the broad range of PTSD symptomatology. Combining information from numerous such models may prove a more efficient strategy. © 2005 Elsevier B.V. All rights reserved.
author list (cited authors)
Liberzon, I., Khan, S., & Young, E. A.
Handbook of Stress and the Brain - Part 2: Stress: Integrative and Clinical Aspects