Discussion
Previous work has identified the MMP9 inhibiting drug doxycycline as a possible inhibitor of human fear memory consolidation (First, a likely conclusion from our study is that doxycycline has a smaller than anticipated – or no – impact on trace fear conditioning. This null finding contrasts with previous work on delay fear conditioning (Second, results from parallel methodological work and the current placebo group indicated that our preregistered and exploratory analyses were unexpectedly underpowered. Effect size to measure trace fear memory retention was smaller in the present placebo group (Cohen’s Finally, we found no evidence that shortcomings in experimental methodology account for the null result. We verified that in keeping with our previous work (Our approach to treatment development was based on preventing fear memory consolidation; but there are also other strategies. A somewhat related approach is to interfere with the reconsolidation of already-consolidated memory which relies on a similar molecular signaling cascade (To conclude, we found no evidence that doxycycline impacts on long-interval trace fear conditioning. Unexpectedly, effect sizes in our paradigm were generally low in several independent control samples, to the extent that replication studies with sufficient power might be impractical because of the required sample size (Acknowledgments: We thank Tamara Grossrieder, Julia Kapfer, Soraya Marques, Timothy Obergfell, Julia Schäfer, Léonie Seys, and Sarrina Tursunova for their help in data acquisition and Samuel Gerster for technical support.