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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    • "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.
    ILAR journal / National Research Council, Institute of Laboratory Animal Resources 09/2014; 55(2):246-258. DOI:10.1093/ilar/ilu008 · 2.39 Impact Factor
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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.
    Frontiers in Behavioral Neuroscience 06/2012; 6:26. DOI:10.3389/fnbeh.2012.00026 · 3.27 Impact Factor
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    • "However, there are also notable differences. Exposing animals to brief uncontrollable and chronic stress prior to fear conditioning, or conducting fear conditioning in animals that are vulnerable to stress, enhances cued conditioned responding during fear conditioning and/or fear extinction (Izquierdo et al. 2006; Miracle et al. 2006; Goswami et al. 2010; Wilber et al. 2011), which suggests that stress-induced changes in fear memory may contribute to changes in extinction retention. This interpretation is also supported by the observation that, when the cue and the footshock presentations are not explicitly paired during fear conditioning (i.e., pseudoconditioning), chronic stress pre-exposure has no effect on extinction retention (Baran et al. 2009; Wilber et al. 2011). "
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    ABSTRACT: Clinical research has linked post-traumatic stress disorder (PTSD) with deficits in fear extinction. However, it is not clear whether these deficits result from stress-related changes in the acquisition or retention of extinction or in the regulation of extinction memories by context, for example. In this study, we used the single prolonged stress (SPS) animal model of PTSD and fear conditioning procedures to examine the effects of prior traumatic stress on the acquisition, retention, and context-specificity of extinction. SPS administered one week prior to fear conditioning had no effect on the acquisition of fear conditioning or extinction but disrupted the retention of extinction memories for both contextual and cued fear. This SPS effect required a post-stress incubation period to manifest. The results demonstrate that SPS disrupts extinction retention, leading to enhanced fear renewal; further research is needed to identify the neurobiological processes through which SPS induces these effects.
    Learning & memory (Cold Spring Harbor, N.Y.) 01/2012; 19(2):43-9. DOI:10.1101/lm.024356.111 · 3.66 Impact Factor
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