Post-extinction L-DOPA administration to reduce the return of fear in humans

The dopamine precursor L-DOPA is a promising adjunct to exposure therapy in anxiety disorders. In two magnetic resonance imaging (MRI) studies we previously showed that a post-extinction administration of L-DOPA reduces the return of fear. However, when aiming to replicate these results outside the MRI scanner, we found weaker effects – albeit with an adjusted paradigm. In order to discern whether the discrepant results can be explained by the experimental environment (in- vs. outside MRI scanner) or the differences in the paradigms, we here replicated a previous MRI paradigm outside the MRI scanner. In total, N=50 male participants underwent fear conditioning on day 1 and extinction on day 2. We tested the effect of post-extinction L-DOPA compared to placebo administration on differential skin conductance responses (SCR) during test on day 3. In contrast to previous findings in the MRI scanner, there was no reduction of differential SCRs after L-DOPA compared to placebo intake at test. Resembling previous findings outside the MRI scanner, there was a significant relationship between differential SCRs at the end of extinction on day 2 and test on day 3 in the L-DOPA group. This relationship did, however, not differ between groups. Summarizing, our results rather speak against an effect of paradigm and in favour of an effect of MRI environment. Contextual arousal, likely to be elevated in the MRI environment, may influence the effect of L-DOPA. These findings call for future work to investigate the interaction between arousal and catecholamines in the context of extinction memory consolidation.