Reinstatement of extinguished fear by an unextinguished conditional stimulus

Department of Psychology, University of California at Los Angeles, Los Angeles, CA, USA.
Frontiers in Behavioral Neuroscience (Impact Factor: 3.27). 05/2012; 6:18. DOI: 10.3389/fnbeh.2012.00018
Source: PubMed


Anxiety disorders are often treated using extinction-based exposure therapy, but relapse is common and can occur as a result of reinstatement, whereby an aversive "trigger" can reinstate extinguished fear. Animal models of reinstatement commonly utilize a Pavlovian fear conditioning procedure, in which subjects are first trained to fear a conditional stimulus (CS) by pairing it with an aversive unconditional stimulus (US), and then extinguished by repeated presentations of the CS alone. Reinstatement is typically induced by exposing subjects to an aversive US after extinction, but here we show that exposure to a non-extinguished CS can reinstate conditional fear responding to an extinguished CS, a phenomenon we refer to as "conditional reinstatement" (CRI). Rats were trained to fear two CSs (light and tone) and subsequently underwent extinction training to only one CS (counterbalanced). Presenting the unextinguished CS (but not a novel cue) immediately after extinction reinstated conditional fear responding to the extinguished CS in a test session given 24 h later. These findings indicate that reinstatement of extinguished fear can be triggered by exposure to conditional as well as unconditional aversive stimuli, and this may help to explain why relapse is common following clinical extinction therapy in humans. Further study of CRI using animal models may prove useful for developing refined extinction therapies that are more resistant to reinstatement.

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Available from: Michael Fanselow, Sep 30, 2015
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    • "Recent reports indicate that exposure of rats to cues or contexts that have been independently associated with an aversive US can induce reinstatement. For example, Halladay et al. (2012) have reported that presentation of a nonextinguished CS will reinstate fear to an extinguished CS. Similarly, Morris et al. (2005a,b) found that brief exposure of rats to a shock-associated context—minutes before presenting an extinguished CS in a separate testing context—reinstated fear to the CS. "
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    ABSTRACT: Aversive events can trigger relapse of extinguished fear memories, presenting a major challenge to the long-term efficacy of therapeutic interventions. Here, we examined factors regulating the relapse of extinguished fear after exposure of rats to a dangerous context. Rats received unsignaled shock in a distinct context ("dangerous" context) 24 h prior to auditory fear conditioning in another context. Fear to the auditory conditioned stimulus (CS) was subsequently extinguished either in the conditioning context ("ambiguous" context) or in a third novel context ("safe" context). Exposure to the dangerous context 30 min before a CS retention test caused relapse to the CS in the ambiguous and safe test contexts relative to nonextinguished controls. When rats were tested 24 h later (with or without short-term testing), rats tested in the ambiguous context continued to exhibit relapse, whereas rats tested in the safe context did not. Additionally, exposure of rats to the conditioning context-in place of the unsignaled shock context-did not result in relapse of fear to the CS in the safe testing context. Our work highlights the vulnerabilities of extinction recall to interference, and demonstrates the importance of context associations in the relapse of fear after extinction. © 2015 Goode et al.; Published by Cold Spring Harbor Laboratory Press.
    Learning & memory (Cold Spring Harbor, N.Y.) 03/2015; 22(3):170-8. DOI:10.1101/lm.037028.114 · 3.66 Impact Factor
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    • "rris and colleagues ( 2005b ) demonstrated that artificial induction of adrenergic activity with acute systemic administration of epinephrine replicated the effects of exposure to the dangerous context . Thus , rein - statement of fear to an extinguished CS may be related to the stress engendered by other unsignaled footshocks or fear in general ( Halladay et al . 2012 ; McCarty and Kopin 1978 ; Morris et al . 2005b ) . By this view , any aversive experience might result in the reinstatement of extinguished fear . Whether stress - induced relapse and reinstatement are mediated by overlapping neural structures has yet to be fully explored . If there is overlap , behavioral and pharmacological strategie"
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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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    • "The applied software settings were quite variable, with motion thresholds ranging from 18 to 150, and a minimum freeze duration of less than 1 s up to 3 s. Some authors used settings that were previously optimized for mice (Anagnostaras et al., 2010; Halladay et al., 2012; Beeman et al., 2013; Broadwater and Spear, 2013a,b), while others performed their own validations for rats (Zelikowsky et al., 2012b). Although not mentioned in their papers, several researchers reported to us that they optimized their parameters as well. "
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    ABSTRACT: Behavioral neuroscience is relying more and more on automated behavior assessment, which is often more time-efficient and objective than manual scoring by a human observer. However, parameter adjustment and calibration are a trial-and-error process that requires careful fine-tuning in order to obtain reliable software scores in each context configuration. In this paper, we will pinpoint some caveats regarding the choice of parameters, and give an overview of our own and other researchers' experience with widely used behavioral assessment software. We conclude that, although each researcher should weigh the pros and cons of relying on software vs. manual scoring, we should be aware of possible divergence between both scores, which might be especially relevant when dealing with subtle behavioral effects, like for example in generalization or genetic research.
    Frontiers in Behavioral Neuroscience 02/2014; 8:28. DOI:10.3389/fnbeh.2014.00028 · 3.27 Impact Factor
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