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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Available from: Michael Fanselow, Oct 03, 2015
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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
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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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    • "Fear conditioning is a well-characterized and widely studied phenomenon. It occurs when an animal is exposed to an aversive stimulus and an unconditioned fear response becomes associated with an environmental cue such as the context in which the aversive stimuli occurred [4] [5]. Fear conditioning is typically studied by placing an animal in a conditioning chamber (e.g. "
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    ABSTRACT: Repeated exposure to laboratory stressors often results in behavioral changes that are commonly referred to as depressive-like behaviors. Here, we examined the contribution fear conditioning may play in altering an animals' behavior in a repeated stress paradigm. Fischer rats were exposed daily to different stressors in a complex environment (context A). After four days of stressor exposure, exploratory behavior (10 min in new cage) and social interaction (5 min with juvenile) were tested on day 5 in either the same environment or a new environment (context B). Rats showed decreased exploration and social interaction when tested in context A compared to control rats or rats tested in context B. Additionally, chronic infusion of propranolol (beta-adrenergic receptor antagonist that crosses the blood-brain barrier), but not nadolol (beta-adrenergic receptor antagonist that does not readily cross the blood-brain barrier), prevented the behavioral changes following repeated stressor exposure. Propranolol treatment did not affect the acute or chronic elevation of corticosterone, the decrease in body weight gain, or adrenal hypertrophy observed in animals exposed to stress. These data demonstrate that conditioned fear responses can contribute to behavioral changes in a repeated stress paradigm. Additional studies revealed, Sprague-Dawley rats do not demonstrate decreased exploration or social interaction when testing occurs in the same context as repeated stressor exposure suggesting Fischer rats may have a greater propensity to associate distal cues with aversive events in a complex environment. This may be due to greater stress responses in Fischer animals that are known to enhance consolidation of emotionally arousing events.
    Behavioural brain research 06/2012; 233(2):536-44. DOI:10.1016/j.bbr.2012.05.040 · 3.03 Impact Factor
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