Upon recall a memory can enter a labile state in which

Upon recall a memory can enter a labile state in which it requires new protein synthesis to restabilize. is typically demonstrated in animals through the amnestic effects of protein synthesis inhibitors administered after memory reactivation (e.g. Nader et al. 2000 Sara 2000 In a series of human fear conditioning studies in our lab we convincingly demonstrated that administration of the β-adrenergic receptor antagonist propranolol HCl or memory reactivation eliminated the emotional expression of fear memory (i.e. fear potentiated startle reflex) while leaving the declarative memory intact (Kindt et al. 2009 Soeter and Kindt 2010 2011 2012 b; Sevenster et al. 2012 2013 2014 Importantly this fear-reducing effect was long-lasting (Soeter and Kindt 2010 and generalized to semantically related stimuli (Soeter and Kindt 2011 2012 as well as to other contexts (Soeter and Kindt 2012 These findings mark the potential of disrupting reconsolidation with propranolol to weaken and perhaps even erase a previously learned fear response. Reconsolidation has been shown across several species and with different protocols which underlines the robustness of this phenomenon. However there are also certain parameters – so-called boundary conditions – that may constrain reconsolidation to occur (Nader and Hardt 2009 Recently it has been shown that mere retrieval is not sufficient to render a memory trace labile (Pedreira et al. 2004 Sevenster et al. 2012 2013 2014 Díaz-Mataix et al. 2013 A prerequisite to trigger Torin 2 reconsolidation is the experience of a prediction error upon retrieval which refers to a mismatch between what is expected and the actual experience. Other putative boundary conditions that have been proposed are Torin 2 the strength (Suzuki et al. 2004 Wang et al. 2009 but see Soeter and Kindt 2012 and the age (Milekic and Alberini 2002 Suzuki et al. 2004 of the consolidated memory trace repetitive or prolonged memory reactivation (i.e. extinction learning) (e.g. Eisenberg et al. 2003 Bos et al. 2012 Sevenster et al. 2014 and the spatial context during memory reactivation (Hupbach et al. 2008 Thus memory reconsolidation upon retrieval may only occur under the appropriate conditions. The effectiveness of disrupting memory reconsolidation seems to be sensitive to individual differences as well such as genetic polymorphisms FHF1 (Agren et al. 2012 and trait anxiety (Soeter and Kindt 2013 Collapsing the data of most of our previous experiments revealed that individuals that can be characterized by high levels of trait anxiety showed somewhat less fear reduction following propranolol HCl administration or memory reactivation. This may indicate that for individuals high in trait anxiety either another reactivation procedure or higher doses of propranolol HCl are required to trigger or interfere with the process of fear memory reconsolidation (Soeter and Kindt 2013 The ability to eliminate Torin 2 the emotional expression of fear memory by disrupting memory reconsolidation may substantially enhance treatment efficacy in the near future. To apply this procedure in clinical practice it is however essential to understand the optimal and boundary conditions of this procedure. The reported data in this article were part of a larger project aimed at unraveling putative boundary conditions of disrupting reconsolidation of memory in humans with propranolol HCl. The project started with pilot studies to demonstrate our reconsolidation effect but turned out in a failure to replicate our previous findings. Along the way we made subtle changes in our instructions in order to optimize the procedure. It bears mentioning that we have replicated our original finding of disrupting fear memory Torin 2 reconsolidation (Kindt et al. 2009 multiple times (Soeter and Kindt 2010 2011 2012 b; Sevenster et al. 2012 2013 2014 Hence the initial objective of the current study was Torin 2 not to demonstrate another replication. Nevertheless presenting these unexpected results is important as they might at least prevent a publication bias even though it remains unclear why we failed to reduce the conditioned fear response (CR). We report the data of 44 participants who underwent a three-day differential fear conditioning paradigm including the following phases: acquisition (day 1) memory.