Limited replicability of drug-induced amnesia after contextual fear memory retrieval in rats.

With the ultimate goal of investigating boundary conditions for post-reactivation amnesia, we set out to replicate studies in which systemic, post-reactivation administration of midazolam, propranolol, or cycloheximide resulted in amnesia for contextual fear memories. Our experiments involved conceptual as well as exact replications of previously published studies. In most of our experiments, we adopted a procedure that conformed to the standard 3-day protocol typically used in the literature, with contextual fear conditioning on day 1, unreinforced re-exposure to the conditioning context followed by systemic injection of the amnestic drug on day 2, and a memory retention test on day 3. Given the plethora of successful studies with large effects sizes and the absence of any failed replications in the literature, we were surprised to find that we were generally unable to replicate those findings. Our results suggest that post-reactivation amnesia by systemic drug administration in rats is more difficult to obtain than what would be expected based on published empirical reports. At present, it remains unclear which conditions determine the success of this procedure.

Post-weaning housing conditions influence freezing during contextual fear conditioning in adult rats.

The present study aimed to investigate the influence of housing conditions on contextual fear memory malleability. Male Wistar rats were housed in enriched, standard, or impoverished conditions after weaning and remained in these conditions throughout the entire experiment. After six weeks into those housing conditions, all animals underwent a 3-day protocol including contextual fear conditioning (day 1), memory reactivation followed by systemic administration of midazolam or vehicle (day 2), and a retention test (day 3). Percentage freezing was used as a behavioral measure of contextual fear. There was no evidence for an effect of housing conditions on the sensitivity of contextual fear memory to amnestic effects of post-reactivation midazolam administration, and no indication for amnestic effects of post-reactivation midazolam overall (including in the standard group). The inability to replicate previous demonstrations of post-reactivation amnesia using the same protocol underscores the subtle nature of post-reactivation pharmacological memory interference. Notably, impoverished housing resulted in a decrease in contextual freezing during contextual fear conditioning, reactivation and retention testing, compared to enriched and standard housing conditions. This observation warrants caution when interpreting the results from experiments regarding effects of housing on fear memory processes, particularly when freezing is used as a measure of fear.

The elusive nature of the blocking effect: 15 failures to replicate.

With the discovery of the blocking effect, learning theory took a huge leap forward, because blocking provided a crucial clue that surprise is what drives learning. This in turn stimulated the development of novel association-formation theories of learning. Eventually, the ability to explain blocking became nothing short of a touchstone for the validity of any theory of learning, including propositional and other nonassociative theories. The abundance of publications reporting a blocking effect and the importance attributed to it suggest that it is a robust phenomenon. Yet, in the current article we report 15 failures to observe a blocking effect despite the use of procedures that are highly similar or identical to those used in published studies. Those failures raise doubts regarding the canonical nature of the blocking effect and call for a reevaluation of the central status of blocking in theories of learning. They may also illustrate how publication bias influences our perspective toward the robustness and reliability of seemingly established effects in the psychological literature. (PsycINFO Database Record