Reactivation-dependent amnesia for contextual fear memories: Evidence for publication bias

Research on memory reconsolidation has been booming in the last two decades, with numerous high-impact publications reporting promising amnestic interventions in rodents and humans. However, our own recently published failed replication attempts of reactivation-dependent amnesia for fear memories in rats suggest that such amnestic effects are not always readily found and that they depend on subtle and possibly uncontrollable parameters. The discrepancy between our observations and published studies in rodents suggests that the literature in this field might be biased. The aim of the current study was to gauge the presence of publication bias in a well-delineated part of the reconsolidation literature. To this end, we performed a systematic review of the literature on reactivation-dependent amnesia for contextual fear memories in rodents, followed by a statistical assessment of publication bias in this sample. In addition, relevant researchers were contacted for unpublished results, which were included in the current analyses. The obtained results support the presence of publication bias, suggesting that the literature provides an overly optimistic overall estimate of the size and reproducibility of amnestic effects. Reactivation-dependent amnesia for contextual fear memories in rodents is thus less robust than what is projected by the literature. The moderate success of clinical studies may be in line with this conclusion, rather than reflecting translational issues. For the field to evolve, replication and non biased publication of obtained results are essential. A set of tools that can create opportunities to increase transparency, reproducibility and credibility of research findings is provided. SIGNIFICANCE STATEMENT The present study suggests that the literature on drug-induced, reactivation-dependent amnesia for contextual fear memories in rodents is biased. Such bias is problematic because it can misinform researchers when making decisions on how to optimally invest their resources. The lack of robustness of amnestic effects, in combination with the strict (but vague) conditions that are required for memory destabilization and the absence of clear explanations for some of the observed null effects, casts doubt on the potential of the proposed clinical application of post-reactivation interventions. Finally, current mechanistic theories that are commonly used to explain reactivation-dependent amnesia, such as reconsolidation or state-dependency, cannot predict when amnestic effects will occur.