Trait salivary alpha-amylase activity levels define the conditions for facilitation by L-DOPA of extinction consolidation

Even after successful extinction, conditioned fear can return. Strengthening the consolidation of the fear-inhibitory safety memory formed during extinction is one way to counteract return of fear. In this preregistered direct replication study in male participants, we confirm that spontaneous post-extinction reactivations of a neural activation pattern evoked in the ventromedial prefrontal cortex (vmPFC) during extinction predict extinction memory retrieval 24 h later. We do not confirm that L-DOPA administration after extinction enhances retrieval and that this is mediated by enhancement of the number of vmPFC reactivations. However, additional non-preregistered analyses reveal a beneficial effect of L-DOPA on extinction retrieval when controlling for the trait-like stable baseline levels of salivary alpha-amylase enzymatic activity (trait sAA) levels that participants show on the three experimental days. Further, trait sAA negatively predicts retrieval, and this effect is rescued by L-DOPA treatment. Our results suggest that individuals with high basal levels of sympathetic nervous system (SNS) activity may have poor extinction and that L-DOPA may be selectively beneficial for these individuals, which holds potential for clinical applications.