Rau V, DeCola JP, Fanselow MS. Stress-induced enhancement of fear learning: an animal model of posttraumatic stress disorder. Neurosci Biobehav Rev 29: 1207-1223

Department of Psychology, University of California, Los Angeles, 415 Hilgard Ave, Los Angeles, CA 90095-1563, USA.
Neuroscience & Biobehavioral Reviews (Impact Factor: 8.8). 02/2005; 29(8):1207-23. DOI: 10.1016/j.neubiorev.2005.04.010
Source: PubMed


Fear is an adaptive response that initiates defensive behavior to protect animals and humans from danger. However, anxiety disorders, such as Posttraumatic Stress Disorder (PTSD), can occur when fear is inappropriately regulated. Fear conditioning can be used to study aspects of PTSD, and we have developed a model in which pre-exposure to a stressor of repeated footshock enhances conditional fear responding to a single context-shock pairing. The experiments in this chapter address interpretations of this effect including generalization and summation or fear, inflation, and altered pain sensitivity. The results of these experiments lead to the conclusion that pre-exposure to shock sensitizes conditional fear responding to similar less intense stressors. This sensitization effect resists exposure therapy (extinction) and amnestic (NMDA antagonist) treatment. The pattern predicts why in PTSD patients, mild stressors cause reactions more appropriate for the original traumatic stressor and why new fears are so readily formed in these patients. This model can facilitate the study of neurobiological mechanisms underlying sensitization of responses observed in PTSD.

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Available from: Michael Fanselow, Jan 27, 2015
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    • "In preclinical models of PTSD, exposure to uncontrollable traumatic stress leads to enhanced fear conditioning, expression, and interference with extinction (Rau et al., 2005; Baratta et al., 2007, 2008, 2015). Uncontrollable stress triggers a release of serotonin (5-HT) in the brain, specifically in regions known to modulate fear learning and recall including the medial prefrontal cortex (Kawahara et al., 1993; Bland et al., 2003), basolateral amygdala (Kawahara et al., 1993; Amat et al., 1998b) and hippocampus (Amat et al., 1998a). "
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    ABSTRACT: Ethical statement: John P. Christianson and Allison R. Foilb, the authors, verify that animal research was carried out in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 80-23) and all procedures involving animals were reviewed and approved by the Boston College Animal Care and Use Committee. All efforts were made to limit the number of animals used and their suffering.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 09/2015; DOI:10.1016/j.pnpbp.2015.08.017 · 3.69 Impact Factor
    • "Mean (+SEM) percentage of freezing during the Context B test on day 3. Animals not shocked in Context B showed minimal levels of freezing in Context B. Animals not shocked in Context A and given one shock in Context B showed moderate levels of freezing while animals shocked in both contexts showed a reliably higher percentage of freezing compared to the other groups. (Adapted from Rau et al. 2005 "
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    ABSTRACT: In this review, we discuss the usefulness of the distinction between fear and anxiety. The clinical use of the labels is ambiguous, often defining one in terms of the other. We first consider what a useful, objective, and scientifically valid definition would entail and then evaluate several fear/anxiety distinctions that have been made in the neurobiological literature. A strong distinction should specify the difference in conditions that lead to fear versus anxiety. Additionally, fear and anxiety should generate distinct sets of behaviors. Ideally, the two states should be supported by distinguishable neuroanatomical circuits. Such a conceptualization would be consistent with the National Institute of Mental Health's Research Domain Criteria (RDoc). The majority of neurobiological approaches to the fear versus anxiety distinction fail to differentiate the two states in terms of behavior, often using the exact same behavioral measures as indicators. Of the two that do, only Predatory Imminence Theory provides a distinction both in terms of cause and effect. Indeed, that approach provides a ready distinction of anxiety, fear, and panic in terms of both antecedent conditions and response selection rules. Additionally, it appeals to distinct neural circuits to generate these modes of action. © 2015 Perusini and Fanselow; Published by Cold Spring Harbor Laboratory Press.
    Learning & memory (Cold Spring Harbor, N.Y.) 09/2015; 22(9):417-25. DOI:10.1101/lm.039180.115 · 3.66 Impact Factor
    • "These data strongly indicate that animals are still more susceptible to novel stressors, but the long-lasting effect of prior severe stress could not be evident unless a new challenge has to be faced. Similarly, a single inescapable foot-shock or tail-shock session has been demonstrated to enhance foot shock-induced fear conditioning for several days after the inescapable footshocks (Baratta et al., 2007; Rau et al., 2005). In some cases, the impact of a prior stress is only observed after an incubation period of several days (typically one week), suggesting some kind of slowly progressing phenomenon (Pamplona et al., 2011). "
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    ABSTRACT: Exposure to certain acute and chronic stressors results in an immediate behavioral and physiological response to the situation followed by a period of days when cross-sensitization to further novel stressors is observed. Cross-sensitization affects to different behavioral and physiological systems, more particularly to the hypothalamus-pituitary-adrenal (HPA) axis. It appears that the nature of the initial (triggering) stressor plays a major role, HPA cross-sensitization being more widely observed with systemic or high-intensity emotional stressors. Less important appears to be the nature of the novel (challenging) stressor, although HPA cross-sensitization is better observed with short duration (5–15 min) challenging stressors. In some studies with acute immune stressors, HPA sensitization appears to develop over time (incubation), but most results indicate a strong initial sensitization that progressively declines over the days. Sensitization can affect other physiological system (i.e. plasma catecholamines, brain monoamines), but it is not a general phenomenon. When studied concurrently, behavioral sensitization appears to persist longer than that of the HPA axis, a finding of interest regarding long-term consequences of traumatic stress. In many cases, behavioral and physiological consequences of prior stress can only be observed following imposition of a new stressor, suggesting long-term latent effects of the initial exposure.
    Stress (Amsterdam, Netherlands) 08/2015; DOI:10.3109/10253890.2015.1067678 · 2.72 Impact Factor
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