Testing the Return of Fear after a Reconsolidation Manipulation of Fear Memory

Fear extinction is not permanent but is instead more vulnerable than the original fear memory, as traditionally shown by the return of fear phenomena. Because of this, techniques to mitigate the return of fear are needed in the clinical treatment of related psychological conditions. One promising strategy is the occasional reinforced extinction treatment, introducing a gradual and sparse number of CS-US pairings within the extinction treatment. We present the results of three experiments in which we used a threat conditioning procedure in humans. Our main aim was to evaluate whether occasional reinforced extinction could reduce two different forms of relapse: spontaneous recovery (Experiments 1 and 2) and reinstatement (Experiment 3). Contrary to our predictions and previous literature, the results indicate that an occasional reinforcement treatment did not mitigate relapse compared with standard extinction. From a theoretical standpoint, these results are more consistent with the idea that extinction entails the acquisition of new knowledge than with the idea that there are conditions in which extinction leads to a weakening of the original fear memory. These findings also question the generality of the potential benefits of using occasional reinforced extinction in clinical settings.

Download Full-text

Propranolol-induced inhibition of unconditioned stimulus-reactivated fear memory prevents the return of fear in humans

Translational Psychiatry ◽

10.1038/s41398-020-01023-w ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Jiahui Deng ◽

Le Shi ◽

Kai Yuan ◽

Ping Yao ◽

Sijing Chen ◽

...

Keyword(s):

Unconditioned Stimulus ◽

Memory Retrieval ◽

Adrenergic Receptor ◽

Fear Memory ◽

Fear Response ◽

Return Of Fear ◽

The Us ◽

Propranolol Administration ◽

Retrieval Interference ◽

Oral Propranolol

Abstract Fear memories can be reactivated by a fear-associated conditioned stimulus (CS) or unconditioned stimulus (US) and then undergo reconsolidation. Propranolol administration during CS retrieval-induced reconsolidation can impair fear memory that is specific to the reactivated CS. However, from a practical perspective, the US is often associated with multiple CSs, and each CS can induce a fear response. The present study sought to develop and test a US-based memory retrieval interference procedure with propranolol to disrupt the original fear memory and eliminate all CS-associated fear responses in humans. We recruited 127 young healthy volunteers and conducted three experiments. All of the subjects acquired fear conditioning, after which they received the β-adrenergic receptor antagonist propranolol (40 mg) or placebo (vitamin C) and were exposed to the US or CS to reactivate the original fear memory. Fear responses were measured. Oral propranolol administration 1 h before US retrieval significantly decreased subsequent fear responses and disrupted associations between all CSs and the US. However, propranolol administration before CS retrieval only inhibited the fear memory that was related to the reactivated CS. Moreover, the propranolol-induced inhibition of fear memory reconsolidation that was retrieved by the US had a relatively long-lasting effect (at least 2 weeks) and was also effective for remote fear memory. These findings indicate that the US-based memory retrieval interference procedure with propranolol can permanently decrease the fear response and prevent the return of fear for all CSs in humans. This procedure may open new avenues for treating fear-related disorders.

Download Full-text

An Unconditioned Stimulus Retrieval Extinction Procedure to Prevent the Return of Fear Memory

Biological Psychiatry ◽

10.1016/j.biopsych.2014.03.027 ◽

2014 ◽

Vol 76 (11) ◽

pp. 895-901 ◽

Cited By ~ 59

Author(s):

Jianfeng Liu ◽

Liyan Zhao ◽

Yanxue Xue ◽

Jie Shi ◽

Lin Suo ◽

...

Keyword(s):

Unconditioned Stimulus ◽

Fear Memory ◽

Extinction Procedure ◽

Return Of Fear

Download Full-text

Scopolamine blocks context-dependent reinstatement of fear responses in rats

10.1101/2021.02.24.432279 ◽

2021 ◽

Author(s):

Laura M. Vercammen ◽

Adrian C. Lo ◽

Rudi D’Hooge ◽

Bram Vervliet

Keyword(s):

Receptor Antagonist ◽

Muscarinic Receptor ◽

Experimental Research ◽

Total Sample ◽

Fear Memory ◽

Systemic Administration ◽

Female Rats ◽

Acquisition Session ◽

Return Of Fear ◽

Context Dependent

AbstractReturn of fear poses a problem for extinction-based therapies of clinical anxiety. Experimental research has discovered several pathways to return of fear, one of which is known as reinstatement. Here, we evaluated in rats the potential of scopolamine, a non-selective muscarinic receptor antagonist that is also safe for use in humans, to prevent the reinstatement of extinguished fear. We conducted three experiments with a total sample of 96 female rats. All rats went through a fear acquisition session (tone-shock pairings, CS-US), followed by two extinction sessions (CS only) and a post-extinction fear memory test. Twenty-four hours later, rats were placed in the same or a different context from extinction and received two unsignaled foot shock (US) presentations. On the following day, CS-evoked freezing returned when the reinstating USs had occurred in the same context compared to a different context (context-dependent reinstatement, Experiment 1). Systemic administration of scopolamine before or after the reinstating USs blocked the return of CS-evoked freezing on the following day (Experiments 2 and 3). Our findings suggest that administering scopolamine around the time of an aversive experience could prevent relapse of extinguished fears in humans.

Download Full-text