Abstract
RationaleA promising strategy to prevent a return of fear after exposure-based therapy in anxiety disorders is to pharmacologically enhance the extinction memory consolidation presumed to occur after exposure. Accumulating evidence suggests that the effect of a number of pharmacological consolidation enhancers depends on a successful fear reduction during exposure. Here, we employed the dopamine precursor L-DOPA to clarify whether its documented potential to enhance extinction memory consolidation is dependent on successful fear extinction.MethodsIn two double-blind, randomized and placebo-controlled experiments (experiment 1: N = 79, experiment 2: N = 32) comprising fear conditioning (day 1), extinction followed by administration of 150 mg L-DOPA or placebo (day 2) and a memory test (day 3) in healthy male adults, conditioned responses were assessed as differential skin conductance responses. We tested whether the effect of L-DOPA on conditioned responses at test depended on conditioned responses at the end of extinction in an experiment with a short (10 trials, experiment 1) and long (25 trials, experiment 2) extinction session.ResultsIn both experiments, the effect of L-DOPA was dependent on conditioned responses at the end of extinction. That is, post-extinction L-DOPA compared to placebo administration reduced conditioned responses at test only in participants showing a complete reduction of conditioned fear at the end of extinction.ConclusionThe results support the potential use of L-DOPA as a pharmacological adjunct to exposure treatment, but point towards a common boundary condition for pharmacological consolidation enhancers: a successful reduction of fear in the exposure session.
Highlights
Exposure-based treatments are rooted in the principles of fear extinction and are an initially very effective intervention to reduce pathological fear and anxiety in the context of cognitive-behavioural therapy (Beck et al 2005)
During fear extinction in the laboratory a conditioned stimulus (CS) that was previously paired with an aversive unconditioned stimulus (US) is repeatedly presented in the absence of the US, resulting in a reduction of conditioned fear responses (CRs)
The occurrence of a return of fear after extinction indicates that extinction learning does not erase the initial ‘CS-US’ association, but rather creates a competing ‘CS-noUS’ association, or extinction memory, that is suggested to inhibit the expression of fear (Bouton 2004)
Summary
Exposure-based treatments are rooted in the principles of fear extinction and are an initially very effective intervention to reduce pathological fear and anxiety in the context of cognitive-behavioural therapy (Beck et al 2005). The experience that no actual harm occurs during the exposure to the feared stimulus or situation results in a reduction of pathological fear and anxiety (Craske et al 2008; Craske et al 2014). During fear extinction in the laboratory a conditioned stimulus (CS) that was previously paired with an aversive unconditioned stimulus (US) is repeatedly presented in the absence of the US, resulting in a reduction of conditioned fear responses (CRs). In both laboratory settings and in clinical practice CRs can, be re-evoked. In order to ensure a reliable long-term reduction of fear after extinction learning or exposure treatment, the extinction memory trace has to be reliably retrieved upon a new encounter with the CS despite competition with the fear memory trace
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