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How Administration of the Beta-Blocker Propranolol Before Extinction can Prevent the Return of Fear.

ABSTRACT: Combining beta-blockers with exposure therapy has been advocated to reduce fear, yet experimental studies combining beta-blockers with memory reactivation have had contradictory results. We explored how beta-blockade might affect the course of safety learning and the subsequent return of fear in a double-blind placebo-controlled functional magnetic resonance imaging study in humans (N=46). A single dose of propranolol before extinction learning caused a loss of conditioned fear responses, and prevented the subsequent return of fear and decreased explicit memory for the fearful events in the absence of drug. Fear-related neural responses were persistently attenuated in the dorsal medial prefrontal cortex (dmPFC), increased in the hippocampus 24 h later, and correlated with individual behavioral indices of fear. Prediction error-related responses in the ventral striatum persisted during beta-blockade. We suggest that this pattern of results is most consistent with a model where beta-blockade can prevent the return of fear by (i) reducing retrieval of fear memory, via the dmPFC and (ii) increasing contextual safety learning, via the hippocampus. Our findings suggest that retrieval of fear memory and contextual safety learning form potential mnemonic target mechanisms to optimize exposure-based therapy with beta-blockers.

SUBMITTER: Kroes MC

PROVIDER: S-EPMC4820039 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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How Administration of the Beta-Blocker Propranolol Before Extinction can Prevent the Return of Fear.

Kroes Marijn C W MC Tona Klodiana-Daphne KD den Ouden Hanneke E M HE Vogel Susanne S van Wingen Guido A GA Fernández Guillén G

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20151014 6

Combining beta-blockers with exposure therapy has been advocated to reduce fear, yet experimental studies combining beta-blockers with memory reactivation have had contradictory results. We explored how beta-blockade might affect the course of safety learning and the subsequent return of fear in a double-blind placebo-controlled functional magnetic resonance imaging study in humans (N=46). A single dose of propranolol before extinction learning caused a loss of conditioned fear responses, and pr ...[more]

PMID: 26462618

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Project description:Fear conditioning paradigms are widely used in laboratory settings to discover treatments that enhance memory consolidation and various fear processes (extinction learning, limit return of fear) that are relevant targets of exposure-based therapies. However, traditional lab-based paradigms often use the exact same conditioned stimuli for acquisition and extinction (typically differentiated with a context manipulation), whereas the opposite is true in clinical settings, as exposure therapy rarely (if ever) uses precisely the exact same stimuli from an individual's learning history. Accordingly, this study utilized a novel three-day category-based fear conditioning protocol (that uses categories of non-repeating objects [animals and tools] as conditioned stimuli during fear conditioning and extinction) to determine if aerobic exercise enhances the consolidation of extinction learning (reduces return of fear) and memory (for items encoded during extinction) during subsequent tests of extinction recall. Participants (n=40) completed a fear acquisition (day 1), fear extinction (day 2), and extinction recall (day 3) protocol. On day 1, participants completed a fear acquisition task in which they were trained to associate a category of conditioned stimuli (CS+) with the occurrence of an unconditioned stimulus (US). On day 2, participants were administered a fear extinction procedure during which CS+ and CS- categorical stimuli were presented in absence of the occurrence of the US. After completing the task, participants were randomly assigned to either receive moderate-intensity aerobic exercise (EX) or a light-intensity control (CON) condition. On day 3, participants completed fear recall tests (during which day 1, day 2, and novel CS+ and CS- stimuli were presented). Fear responding was assessed via threat expectancy ratings and skin conductance responses (SCR). During the fear recall tests, the EX group reported significantly lower threat expectancy ratings to the CS+ and CS- and exhibited greater memory of CS+ and CS- stimuli that were previously presented during day 2. There were no significant group differences for SCR. These results suggests that administration of moderate-intensity aerobic exercise following extinction learning contributes to reduced threat expectancies during tests of fear recall and enhanced memory of items encoded during extinction.

Dataset Information

How Administration of the Beta-Blocker Propranolol Before Extinction can Prevent the Return of Fear.

Publications

How Administration of the Beta-Blocker Propranolol Before Extinction can Prevent the Return of Fear.

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