Rau V, Fanselow MS. Exposure to a stressor produces a long lasting enhancement of fear learning in rats. Stress 12: 125-133

Department of Anesthesia, University of California, San Francisco, CA 94143, USA.
Stress (Amsterdam, Netherlands) (Impact Factor: 2.72). 07/2008; 12(2):125-33. DOI: 10.1080/10253890802137320
Source: PubMed


In contextual fear conditioning, footshock is given in a context, and re-exposure to this context elicits the conditional defensive response of freezing, a reliable behavioral index of conditional fear. Normally, the amount of contextual freezing is directly proportional to the number of shocks an animal receives in the context. However, pre-exposure to a stressor can produce an enhancement in conditional freezing. Pre-exposure to repeated footshock in one context produces an enhancement of conditional freezing to cues associated with a single shock in a second distinct context. This model of stress-enhanced fear learning (SEFL) can be utilized to study how stress affects learning of future aversive events. The experiments in this paper characterize the magnitude and longevity of SEFL. In the first experiment, the number of footshocks given during the pre-exposure session was varied and conditional fear to the single shock was assessed. Pre-exposure to 1 shock did not produce an enhancement in fear learning in the second context, but pre-exposure to 4 or 15 shocks did. The time-course of the enhancement was examined in the next two experiments. These experiments show that SEFL persists for at least 3 months.

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    • "Given that the effect does not depend on associative factors, it appears to be a nonassociative sensitization of fear learning. This sensitization is extremely persistent ; it is not diminished even when 90 d intervenes between stress and conditioning (Rau and Fanselow 2009; Poulos et al. 2014; Quinn et al. 2014). Maier and Watkins (1998) have suggested that this sensitized state corresponds to anxiety. "
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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
    • "In this model, rats receive a series of 15 shocks, randomly distributed over 90 min. This experience produces behavioral changes lasting at least 90 days unabated (Rau and Fanselow, 2009). After this experience, rats acquire exaggerated contextual and cued fear in novel situations using a single shock. "
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    ABSTRACT: Fear promotes adaptive responses to threats. However, when the level of fear is not proportional to the level of threat, maladaptive fear-related behaviors characteristic of anxiety disorders result. Post-traumatic stress disorder develops in response to a traumatic event, and patients often show sensitized reactions to mild stressors associated with the trauma. Stress-enhanced fear learning (SEFL) is a rodent model of this sensitized responding, in which exposure to a 15-shock stressor nonassociatively enhances subsequent fear conditioning training with only a single trial. We examined the role of corticosterone (CORT) in SEFL. Administration of the CORT synthesis blocker metyrapone prior to the stressor, but not at time points after, attenuated SEFL. Moreover, CORT co-administered with metyrapone rescued SEFL. However, CORT alone without the stressor was not sufficient to produce SEFL. In these same animals, we then looked for correlates of SEFL in terms of changes in excitatory receptor expression. Western blot analysis of the basolateral amygdala (BLA) revealed an increase in the GluA1 AMPA receptor subunit that correlated with SEFL. Thus, CORT is permissive to trauma-induced changes in BLA function.Neuropsychopharmacology advance online publication, 2 September 2015; doi:10.1038/npp.2015.224.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 08/2015; DOI:10.1038/npp.2015.224 · 7.05 Impact Factor
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    • "(A.P. Carobrez). exposure to diverse threatening situations facilitates the encoding of fear memory during acquisition [1] [2] [3] [4]. These reports, in fact, support the widespread notion that emotionally driven experiences results in stronger and long-lasting memories [1,4–6]. "
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    ABSTRACT: The association of a neutral context with an aversive stimulus, such as foot-shock, result in a contextual fear memory. A growing number of evidence have revealed that prior exposure to diverse threatening situations facilitates the encoding of fear memory during acquisition and such reports support the widespread notion that emotionally arousal results in stronger and long-lasting memories. However, few studies have investigated if a threatening experience can affect the recall and the persistence of such fear memory trace. To test the hypothesis that an emotionally negative experience could modify the retrieval of a memory and potentiate the expression of a fear memory, the present study used the chemical stimulation (microinjection of NMDA) of the dorsolateral periaqueductal gray matter (dlPAG) of rats in order to induce an aversive emotional state. Such stimulation was performed one day after a weak fear training protocol, and the fear expression was analyzed in subsequent re-exposures to the conditioned context. The results showed that the negative emotional state induced by the dlPAG stimulation enhanced the fear memory trace when this trace was reactivated one day after this aversive experience. Additionally, the potentiation of the fear response was contingent to the associated context since no potentiation was evident when NMDA-stimulated animals were subsequently placed in a non-associated context. Finally, the model suggests that the enhancement of fear responses is long-lasting since NMDA-treated animals performed a robust fear response six days after memory retrieval.
    Behavioural brain research 09/2012; 237C(1):76-81. DOI:10.1016/j.bbr.2012.09.012 · 3.03 Impact Factor
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