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bioRxiv · 10.1101/2022.11.12.516261

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

Andres, E.·Chuan-Peng, H.·Gerlicher, A. M. V.·Meyer, B.·Tuescher, O.·Kalisch, R.
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Abstract

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.

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Andres, E., Chuan-Peng, H., Gerlicher, A. M. V., Meyer, B., Tuescher, O., Kalisch, R.. 2022-11-14. Arousal defines the conditions for facilitation by L-DOPA of extinction consolidation and associated prefrontal activity. https://doi.org/10.1101/2022.11.12.516261

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