Arousal defines the conditions for facilitation by L-DOPA of extinction consolidation and associated prefrontal activity

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, 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 preregistered analyses reveal a beneficial effect of L-DOPA on extinction retrieval when controlling for salivary alpha-amylase (sAA) levels, an indicator of arousal, at extinction onset. Further, pre-extinction sAA negatively predicts retrieval and (at trend) vmPFC reactivations, and these impeding effects are abolished by L-DOPA treatment. Our results suggest that L-DOPA may enhance extinction consolidation under high-arousal conditions, as typically present during exposure therapy sessions. ### Competing Interest Statement R.K. has received advisory honoraria from JoyVentures, Herzlia, Israel.