Treatments that weaken Pavlovian conditioned fear and thwart its renewal in rats: Implications for treating human phobias.

Rauhut, Anthony S.; Thomas, Brian L.; Ayres, John J. B.

doi:10.1037/0097-7403.27.2.99

Cited by 91 publications

(92 citation statements)

References 34 publications

(51 reference statements)

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“…During later testing, retrieval of the extinction memory is contingent on presenting the CS in the context in which extinction training occurred; outside this context, renewal of fear is observed. This effect has been repeatedly demonstrated in both rats (Bouton and Bolles, 1979;Bouton and Ricker, 1994;Rauhut et al, 2001) and humans (Mineka et al, 1999;Mystkowski et al, 2002). In keeping with well established roles for the hippocampus in forming representations of contexts (Selden et al, 1991;Kim and Fanselow, 1992;Phillips and LeDoux, 1992;Matus-Amat et al, 2004), and using those representations to guide behavior (Frankland et al, 1998;Fanselow, 2000;Maren and Holt, 2000;Rudy and O'Reilly, 2001), mounting evidence suggests a role for the hippocampus in mediating the context-specific retrieval of fear extinction Maren, 2001, 2004).…”

Section: Introductionmentioning

confidence: 90%

Hippocampal Inactivation Disrupts the Acquisition and Contextual Encoding of Fear Extinction

et al. 2005

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In recent studies, inactivation of the dorsal hippocampus before the retrieval of extinguished fear memories disrupted the contextdependent expression of these memories. In the present experiments, we examined the role of the dorsal hippocampus in the acquisition of extinction. After pairing an auditory conditional stimulus (CS) with an aversive footshock [unconditional stimulus (US)], rats received an extinction session in which the CS was presented without the US. In experiment 1, infusion of muscimol, a GABA A receptor agonist, into the dorsal hippocampus before the extinction training session decreased the rate of extinction. Moreover, when later tested for fear to the extinguished CS, all rats that had received hippocampal inactivation before extinction training demonstrated renewed fear regardless of the context in which testing took place. This suggests a role for the dorsal hippocampus in both acquiring the extinction memory and encoding the CS-context relationship that yields the context dependence of extinction. In experiment 2, inactivation of the dorsal hippocampus before testing also disrupted the context dependence of fear to the extinguished CS. In experiment 3, quantitative autoradiography revealed the boundaries of muscimol diffusion after infusion into the dorsal hippocampus. Together, these results reveal that the dorsal hippocampus is involved in the acquisition, contextual encoding, and context-dependent retrieval of fear extinction. Learning and remembering when and where aversive events occur is essential for adaptive emotional regulation.

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Section: Introductionmentioning

confidence: 90%

Hippocampal Inactivation Disrupts the Acquisition and Contextual Encoding of Fear Extinction

et al. 2005

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“…35 Thus, rather than learning that 'now the cue is no longer paired with the shock', the animal learns that 'now, in this place, the cue is no longer paired with the shock'. There is some debate as to whether renewal may be mitigated by overtraining of extinction 36,37 or extinction in multiple contexts. [38][39][40][41] Spontaneous recovery.…”

Section: Behavioral and Theoretical Considerationsmentioning

confidence: 99%

Mechanisms of fear extinction

2006

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Excessive fear and anxiety are hallmarks of a variety of disabling anxiety disorders that affect millions of people throughout the world. Hence, a greater understanding of the brain mechanisms involved in the inhibition of fear and anxiety is attracting increasing interest in the research community. In the laboratory, fear inhibition most often is studied through a procedure in which a previously fear conditioned organism is exposed to a fear-eliciting cue in the absence of any aversive event. This procedure results in a decline in conditioned fear responses that is attributed to a process called fear extinction. Extensive empirical work by behavioral psychologists has revealed basic behavioral characteristics of extinction, and theoretical accounts have emphasized extinction as a form of inhibitory learning as opposed to an erasure of acquired fear. Guided by this work, neuroscientists have begun to dissect the neural mechanisms involved, including the regions in which extinction-related plasticity occurs and the cellular and molecular processes that are engaged. The present paper will cover behavioral, theoretical and neurobiological work, and will conclude with a discussion of clinical implications. Molecular Psychiatry (2007) 12, 120-150.

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“…Importantly, renewal does not seem to be mitigated by overtraining of extinction, meaning that CR return is observed even following extensive extinction training well beyond the point at which behavioral CRs have disappeared (Rauhut et al 2001). Hence, a lack of renewal following shortinterval extinction would be difficult to attribute to facilitated inhibition as opposed to some other mechanism, such as erasure.…”

Section: Experiments 2: Renewalmentioning

confidence: 99%

“…This provides a second, independent piece of evidence that the mechanism of short-interval extinction differs from that of long-interval extinction. Importantly, the lack of significant renewal in the early time-point groups is not easily accounted for by facilitated inhibition, because renewal is known to occur even following extensive overtraining of extinction, a circumstance that would seem to favor the development of an especially strong inhibitory association (Rauhut et al 2001). This then would seem to suggest that the mechanism of short-interval extinction differs qualitatively from that of longinterval extinction, such that it is not due to inhibitory learning but, rather, involves some other mechanism, such as erasure.…”

Section: Experiments 2: Renewalmentioning

confidence: 99%

Different mechanisms of fear extinction dependent on length of time since fear acquisition

Myers

Ressler²,

Davis³

2006

Learn. Mem.

293

267

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Fear extinction is defined as a decline in conditioned fear responses (CRs) following nonreinforced exposure to a feared conditioned stimulus (CS). Behavioral evidence indicates that extinction is a form of inhibitory learning: Extinguished fear responses reappear with the passage of time (spontaneous recovery), a shift of context (renewal), and unsignaled presentations of the unconditioned stimulus (reinstatement). However, there also is evidence to suggest that extinction is an "unlearning" process corresponding to depotentiation of potentiated synapses within the amygdala. Because depotentiation is induced more readily at short intervals following LTP induction and is not inducible at all at a sufficient delay, it may be that extinction initiated shortly following fear acquisition preferentially engages depotentiation/"unlearning," whereas extinction initiated at longer delays recruits a different mechanism. We investigated this possibility through a series of behavioral experiments examining the recoverability of conditioned fear following extinction. Consistent with an inhibitory learning mechanism of extinction, rats extinguished 24-72 h following acquisition exhibited moderate to strong reinstatement, renewal, and spontaneous recovery. In contrast, and consistent with an erasure mechanism, rats extinguished 10 min to 1 h after acquisition exhibited little or no reinstatement, renewal, or spontaneous recovery. These data support a model in which different neural mechanisms are recruited depending on the temporal delay of fear extinction.

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Treatments that weaken Pavlovian conditioned fear and thwart its renewal in rats: Implications for treating human phobias.

Cited by 91 publications

References 34 publications

Hippocampal Inactivation Disrupts the Acquisition and Contextual Encoding of Fear Extinction

Hippocampal Inactivation Disrupts the Acquisition and Contextual Encoding of Fear Extinction

Mechanisms of fear extinction

Different mechanisms of fear extinction dependent on length of time since fear acquisition

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