Impact of predatory threat on fear extinction in Lewis rats

Center for Molecular and Behavioral Neuroscience, Rutgers State University, Newark, New Jersey 07102, USA.
Learning & memory (Cold Spring Harbor, N.Y.) (Impact Factor: 3.66). 09/2010; 17(10):494-501. DOI: 10.1101/lm.1948910
Source: PubMed


Humans with post-traumatic stress disorder (PTSD) are deficient at extinguishing conditioned fear responses. A study of identical twins concluded that this extinction deficit does not predate trauma but develops as a result of trauma. The present study tested whether the Lewis rat model of PTSD reproduces these features of the human syndrome. Lewis rats were subjected to classical auditory fear conditioning before or after exposure to a predatory threat that mimics a type of traumatic stress that leads to PTSD in humans. Exploratory behavior on the elevated plus maze 1 wk after predatory threat exposure was used to distinguish resilient vs. PTSD-like rats. Properties of extinction varied depending on whether fear conditioning and extinction occurred before or after predatory threat. When fear conditioning was carried out after predatory threat, PTSD-like rats showed a marked extinction deficit compared with resilient rats. In contrast, no differences were seen between resilient and PTSD-like rats when fear conditioning and extinction occurred prior to predatory threat. These findings in Lewis rats closely match the results seen in humans with PTSD, thereby suggesting that studies comparing neuronal interactions in resilient vs. at-risk Lewis rats might shed light on the causes and pathophysiology of human PTSD.

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    • "Individual variability is nowadays considered as a critical component of PTSD animal models because it allows identifying predicting factors of resilience or susceptibility to traumatization (Cohen et al., 2012; Goswami et al., 2013; Daskalakis and Yehuda, 2014). Unfortunately, most of the animal models of PTSD currently available do not evaluate individual susceptibility to relapse after successful fear extinction (but see Goswami et al., 2010). In the present manuscript, we pursue to main objectives. "
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    ABSTRACT: Posttraumatic stress disorder (PTSD) is a highly debilitating and prevalent psychological disorder. It is characterized by highly distressing intrusive trauma memories that are partly explained by fear conditioning. Despite efficient therapeutic approaches, a subset of PTSD patients displays spontaneous recurrence of traumatic memories after successful treatment. The development of animal behavioral models mimicking the individual variability in treatment outcome for PTSD patients represent therefore an important challenge as it allows for the identification of predicting factors of resilience or susceptibility to relapse. However, to date, only few animal behavioral models of long-lasting fear recovery have been developed and their predictive validity has not been tested directly. The objectives of this study were twofold. First we aimed to develop a simple animal behavioral model of long-lasting fear recovery based on auditory cued fear conditioning and extinction learning, which recapitulates the heterogeneity of fear responses observed in PTSD patients after successful treatment. Second we aimed at testing the predictive validity of our behavioral model and used to this purpose a translational approach based (i) on the demonstration of the efficiency of Eye Movement Desensitization and Reprocessing (EMDR) therapy to reduce conditioned fear responses in PTSD patients and (ii) on the implementation in our behavioral model of an electrical bilateral alternating stimulation of the eyelid which mimics the core feature of EMDR. Our data indicate that electrical bilateral alternating stimulation of the eyelid during extinction learning alleviates long-lasting fear recovery of conditioned fear responses and dramatically reduces inter-individual variability. These results demonstrate the face and predictive validity of our animal behavioral model and provide an interesting tool to understand the neurobiological underpinnings of long-lasting fear recovery.
    Full-text · Article · Jun 2015 · Neuroscience
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    • "These PTSD - like rats were shown to exhibit low levels of exploratory behavior on an elevated plus maze . Interestingly , Goswami and colleagues ( 2010 ) demonstrated that this impairment in extinction reten - tion was not observed in rats that had previously exhibited high levels of exploratory behavior on the elevated plus maze ( i . e . "
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    ABSTRACT: Whereas fear memories are rapidly acquired and enduring over time, extinction memories are slow to form and are susceptible to disruption. Consequently, behavioral therapies that involve extinction learning (e.g., exposure therapy) often produce only temporary suppression of fear and anxiety. This review focuses on the factors that are known to influence the relapse of extinguished fear. Several phenomena associated with the return of fear after extinction are discussed, including renewal, spontaneous recovery, reacquisition, and reinstatement. Additionally, this review describes recent work, which has focused on the role of psychological stress in the relapse of extinguished fear. Recent developments in behavioral and pharmacological research are examined in light of treatment of pathological fear in humans.
    Full-text · Article · Sep 2014 · ILAR journal / National Research Council, Institute of Laboratory Animal Resources
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    • "Rats that displayed extremely compromised exploratory behavior in the EPM (zero time in the open arms) were classified as " PTSD-like " (44 rats or 54%) whereas rats that explored the open arms for any amount of time were classified as " Resilient " (37 rats or 46%). The incidence of the PTSD-like phenotype in this sample is consistent with that found in previous studies using the same paradigm (45–50%; Cohen et al., 2006a; Goswami et al., 2010), and much higher than in naïve Lewis rats (not subjected to predatory threat; 13%; Goswami et al., 2010). Importantly, by comparing various measures of anxiety in naïve vs. Resilient rats, the latter study determined that predatory threat did not cause a general increase in anxiety expressed by all subjects, but the emergence of extreme behavioral manifestations of anxiety in a subset of susceptible Lewis rats. "
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    ABSTRACT: Despite recent progress, the causes and pathophysiology of post-traumatic stress disorder (PTSD) remain poorly understood, partly because of ethical limitations inherent to human studies. One approach to circumvent this obstacle is to study PTSD in a valid animal model of the human syndrome. In one such model, extreme and long-lasting behavioral manifestations of anxiety develop in a subset of Lewis rats after exposure to an intense predatory threat that mimics the type of life-and-death situation known to precipitate PTSD in humans. This study aimed to assess whether the hippocampus-associated deficits observed in the human syndrome are reproduced in this rodent model. Prior to predatory threat, different groups of rats were each tested on one of three object recognition memory tasks that varied in the types of contextual clues (i.e., that require the hippocampus or not) the rats could use to identify novel items. After task completion, the rats were subjected to predatory threat and, one week later, tested on the elevated plus maze (EPM). Based on their exploratory behavior in the plus maze, rats were then classified as resilient or PTSD-like and their performance on the pre-threat object recognition tasks compared. The performance of PTSD-like rats was inferior to that of resilient rats but only when subjects relied on an allocentric frame of reference to identify novel items, a process thought to be critically dependent on the hippocampus. Therefore, these results suggest that even prior to trauma PTSD-like rats show a deficit in hippocampal-dependent functions, as reported in twin studies of human PTSD.
    Full-text · Article · Jun 2012 · Frontiers in Behavioral Neuroscience
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