Reactivation of the Unconditioned Stimulus Inhibits the Return of Fear Independent of Cortisol

Drexler, Shira Meir; Merz, Christian J.; Lissek, Silke; Tegenthoff, Martin; Wolf, Oliver T.

doi:10.3389/fnbeh.2019.00254

Cited by 7 publications

(4 citation statements)

References 69 publications

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“…In contrast, exposure to mild stress led to a fear memory impairment in men (possibly through an interruption of memory reconsolidation: Meir Drexler and Wolf, 2017b). Moreover, while the previous studies used the commonly used CS-based reconsolidation paradigm (i.e., reactivation by a single unreinforced CS presentation), in an alternative UCS-based reconsolidation paradigm (i.e., through a single weaker UCS presentation), the reactivation method itself prevented the return of fear regardless of the pharmacological (cortisol or placebo) treatment (Meir Drexler et al, 2019b).…”

Section: Cortisol and Memory Reconsolidationmentioning

confidence: 99%

Stress modulation of fear and extinction in psychopathology and treatment

et al. 2020

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The glucocorticoid cortisol, a major player in the development of stress-related psychopathology, can also be used for the augmentation of extinction-based psychotherapies (e.g., exposure therapy). Substantial evidence supports its beneficial effects in the treatment of post-traumatic stress disorder and specific phobias. In this review, we first present the role of stress and cortisol in the development of maladaptive emotional memories. Then, we describe the mechanisms that may account for the cortisol-induced augmentation of exposure, namely, the enhancement of extinction memory consolidation and the reduction of the contextual dependency of the extinction memory. Finally, we discuss several considerations and limitations for the use of cortisol in psychotherapy, focusing on the possible adverse effects of cortisol in a reconsolidation-based (as opposed to extinction-based) intervention.

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Section: Cortisol and Memory Reconsolidationmentioning

confidence: 99%

Stress modulation of fear and extinction in psychopathology and treatment

et al. 2020

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“…This indicates that CS exposure renders fear memory vulnerable to the effects of propranolol, thereby reducing fear response. A low-intensity US can also induce prediction errors 34 . We speculate that US retrieval generates larger prediction errors than CS retrieval.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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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.

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“…Building upon these findings, Meir Drexler et al [138] continued investigating the impact of cortisol and US reactivation on fear memory reconsolidation in male participants. The previous findings indicated that differences in cortisol effects on fear memory reconsolidation might exist between men and women.…”

Section: Glucocorticoids and Gender Influence On Fear Extinctionmentioning

confidence: 99%

Targeting Human Glucocorticoid Receptors in Fear Learning: A Multiscale Integrated Approach to Study Functional Connectivity

Battaglia,

Di Fazio,

Mazzà

et al. 2024

IJMS

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Fear extinction is a phenomenon that involves a gradual reduction in conditioned fear responses through repeated exposure to fear-inducing cues. Functional brain connectivity assessments, such as functional magnetic resonance imaging (fMRI), provide valuable insights into how brain regions communicate during these processes. Stress, a ubiquitous aspect of life, influences fear learning and extinction by changing the activity of the amygdala, prefrontal cortex, and hippocampus, leading to enhanced fear responses and/or impaired extinction. Glucocorticoid receptors (GRs) are key to the stress response and show a dual function in fear regulation: while they enhance the consolidation of fear memories, they also facilitate extinction. Accordingly, GR dysregulation is associated with anxiety and mood disorders. Recent advancements in cognitive neuroscience underscore the need for a comprehensive understanding that integrates perspectives from the molecular, cellular, and systems levels. In particular, neuropharmacology provides valuable insights into neurotransmitter and receptor systems, aiding the investigation of mechanisms underlying fear regulation and potential therapeutic targets. A notable player in this context is cortisol, a key stress hormone, which significantly influences both fear memory reconsolidation and extinction processes. Gaining a thorough understanding of these intricate interactions has implications in terms of addressing psychiatric disorders related to stress. This review sheds light on the complex interactions between cognitive processes, emotions, and their neural bases. In this endeavor, our aim is to reshape the comprehension of fear, stress, and their implications for emotional well-being, ultimately aiding in the development of therapeutic interventions.

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Reactivation of the Unconditioned Stimulus Inhibits the Return of Fear Independent of Cortisol

Cited by 7 publications

References 69 publications

Stress modulation of fear and extinction in psychopathology and treatment

Stress modulation of fear and extinction in psychopathology and treatment

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

Targeting Human Glucocorticoid Receptors in Fear Learning: A Multiscale Integrated Approach to Study Functional Connectivity

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