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

Abstract

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.

Lack of drug-induced post-retrieval amnesia for auditory fear memories in rats

“…Inasmuch as we administered all drugs systemically and confined this endeavor to auditory fear memories, our conclusions cannot surpass these procedural choices. Nevertheless, in a recent study, we also described repeated failures to find post-retrieval amnesia in contextual fear conditioning studies with Wistar and Sprague-Dawley rats, using either propranolol or midazolam injections [ 43 ], suggesting that these reproducibility problems may extend to other fear conditioning procedures and pharmacological agents as well.…”

Rats remember: Lack of drug-induced post-retrieval amnesia for auditory fear memories

“…Inasmuch as we administered all drugs systemically and confined this endeavor to auditory fear memories, our conclusions cannot surpass these procedural choices. Nevertheless, in a recent study we also described repeated failures to find post-retrieval amnesia in contextual fear conditioning studies with Wistar and Sprague-Dawley rats, using either propranolol or midazolam injections (Schroyens, Alfei, Schnell, Luyten, & Beckers, 2019), suggesting that these reproducibility problems may extend to other fear conditioning procedures and pharmacological agents as well.…”

A critical assessment of reconsolidation interference as a tool for therapeutic forgetting

“…Rather, they contribute to the flexibility that allows the linking of many behavioral observations to reconsolidation theory. Indeed, in practice, failures to observe an anticipated reconsolidation-dependent effect have typically been attributed to the unintended presence of (unknown) boundary conditions on memory destabilization (e.g., the memory might have been too strong or the amount of prediction error might have been inappropriate, also in our own work (24,74)). The proposed moderators of the effect are thus used to protect reconsolidation theory from being contradicted and can allow researchers to explain away inherently conflicting findings with recourse to reconsolidation theory.…”

“…It has been suggested that not all behavioral effects observed after combining a reminder with an amnestic manipulation can be attributed to reconsolidation interference (7)(8)(9)(10)(11)(12)(13)(14). In addition, there has been a considerable amount of failures to conceptually or exactly replicate previously published studies that appeared to demonstrate memory reconsolidation (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) and reconsolidation theory presently cannot illuminate which factors explain those negative results.…”