Article

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: 4.38). 09/2010; 17(10):494-501. DOI: 10.1101/lm.1948910
Source: PubMed

ABSTRACT 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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    • "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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    • "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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