Reinstatement of fear to an extinguished conditioned stimulus: Two roles for context.

Westbrook, R. Frederick; Iordanova, Mihaela D.; McNally, Gavan P.; Richardson, Rick; Harris, Justin A.

doi:10.1037/0097-7403.28.1.97

Cited by 110 publications

(140 citation statements)

References 21 publications

Supporting

Mentioning

133

Contrasting

Unclassified

Order By: Relevance

“…The rationale was that a CS is familiar or unsurprising by virtue of formation of context-CS associations during initial extinction training (in the case of reextinction) or during preexposure (Wagner, 1981). Such context-CS associations have important implications for learning about and responding to an extinguished CS (Westbrook, Iordanova, McNally, Richardson, & Harris, 2002). If so, then presentation of that CS in a second, different context should have reinstated novelty of the CS and also sensitivity to MK-801.…”

Section: Discussionmentioning

confidence: 99%

Conditioned stimulus familiarity determines effects of MK-801 on fear extinction.

Chan

McNally

2009

Behavioral Neuroscience

View full text Add to dashboard Cite

Six experiments studied the role of conditioned stimulus (CS) familiarity in determining the effects of the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 on fear extinction. Systemic administration of MK-801 (0.1 mg/kg) impaired initial extinction but not reextinction learning. MK-801 impaired reextinction learning when the CS was relatively novel during reextinction training but not initial extinction learning when the CS was relatively familiar during initial extinction training. A context change failed to reinstate the sensitivity of initial fear extinction learning about a relatively familiar CS to MK-801. These experiments show that CS familiarity is an important determinant of effects of MK-801 on fear extinction learning: MK-801 impaired extinction learning about novel stimuli but spared extinction learning about familiar stimuli.

show abstract

Section: Discussionmentioning

confidence: 99%

Conditioned stimulus familiarity determines effects of MK-801 on fear extinction.

Chan

McNally

2009

Behavioral Neuroscience

View full text Add to dashboard Cite

show abstract

“…Other context-dependent mechanisms may contribute as well. 31 Renewal. Renewal refers to a reappearance of extinguished CRs when animals are tested in a context different from the one in which extinction training took place (Figure 1b).…”

Section: Behavioral and Theoretical Considerationsmentioning

confidence: 99%

Mechanisms of fear extinction

2006

View full text Add to dashboard Cite

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.

show abstract

“…This conclusion is based on observations that fear responses can reemerge after unsignaled exposure to the US (reinstatement), following a change in context (renewal), with the passage of time (spontaneous recovery) and that reconditioning occurs faster than initial conditioning (Pavlov, 1927;Rescorla and Heth, 1975;Bouton and Bolles, 1979;Bouton et al, 2006;Robbins, 1990;Westbrook et al, 2002). Further support for this assertion comes from both electrophysiological and psychopharmacological studies of behavioral and synaptic plasticity.…”

Section: Introductionmentioning

confidence: 99%

Disruption of AMPA Receptor Endocytosis Impairs the Extinction, but not Acquisition of Learned Fear

Dalton

Wang

Floresco

et al. 2007

Neuropsychopharmacol

141

135

View full text Add to dashboard Cite

Synaptic plasticity in the form of long-term potentiation (LTP) plays a critical role in the formation of a Pavlovian fear association. However, the role that synaptic plasticity plays in the suppression of a learned fear response remains to be clarified. Here, we assessed the role that long-term depression (LTD) plays in the acquisition, expression, and extinction of a conditioned fear response. We report that blockade of LTD with a GluR2-derived peptide (Tat-GluR2 3Y ; 1.5 mmol/kg, i.v.) that blocks regulated a-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptor endocytosis during an initial extinction training session disrupted both the expression and recall of extinction learning. A similar impairment of extinction during training, but not recall, was observed when NMDA receptor-dependent LTD was inhibited through the selective blockade of NMDA NR2B receptors with Ro 25-6981. In contrast, blockade of LTD with Tat-GluR2 3Y during fear conditioning or during a fear recall test did not effect the expression or recall of either contextual or cue-induced conditioned fear. Similarly, administration of Tat-GluR2 3Y prior to an extinction recall test did not affect spontaneous recovery or rate of re-extinction in previously extinguished rats. These data demonstrate that AMPA receptor endocytosis does not mediate acquisition or expression of conditioned fear, but may play a role in the extinction of fear memories. Furthermore, these findings suggest that LTD may be a molecular mechanism that facilitates the selective modification of a learned association while leaving intact the ability to form a new memory.

show abstract

Reinstatement of fear to an extinguished conditioned stimulus: Two roles for context.

Cited by 110 publications

References 21 publications

Conditioned stimulus familiarity determines effects of MK-801 on fear extinction.

Conditioned stimulus familiarity determines effects of MK-801 on fear extinction.

Mechanisms of fear extinction

Disruption of AMPA Receptor Endocytosis Impairs the Extinction, but not Acquisition of Learned Fear

Contact Info

Product

Resources

About