AbstractWhen retrieved under specific circumstances, consolidated fear memories are thought to return to a labile state, thereby opening a window for modification (e.g., attenuation) of the memory. Several interventions during a critical time frame after this destabilization seem to be able to alter the retrieved memory, for example through pharmacological interference with the restabilization process, either by direct protein synthesis inhibition or indirectly, using drugs that can be safely administered in patients (e.g., propranolol).In a series of well-powered auditory fear conditioning experiments (four with propranolol, 10 mg/kg, two with rapamycin, 20-40 mg/kg, one with anisomycin, 150 mg/kg and cycloheximide, 1.5 mg/kg), we found no evidence for reduced cued fear memory expression during a drug-free test in adult male Sprague-Dawley rats that had previously received a systemic drug injection upon retrieval of the tone fear memory. All experiments used standard fear conditioning and reactivation procedures with freezing as the behavioral read-out (conceptual or exact replications of published reports) and common pharmacological agents. Additional tests confirmed that the applied drug doses and administration routes were effective in inducing their conventional effects on expression of fear (propranolol, acutely), body weight (rapamycin, anisomycin, cycloheximide) and consolidation of extinction memories (cycloheximide).Thus, in contrast with most published studies, we did not find evidence for drug-induced post-retrieval amnesia, underlining that this effect, as well as its clinical applicability, may be considerably more constrained and less readily reproduced than what the current literature would suggest.HighlightsWe aimed to replicate post-retrieval amnesia for auditory fear memories in ratsWe performed a series of well-powered pharmacological interference experimentsPropranolol, rapamycin, anisomycin or cycloheximide was injected upon retrievalBayesian stats found substantial evidence for the absence of post-retrieval amnesiaThe effect is less reproducible and generalizable than what the literature suggests
Multi-site study of an in vivo phototoxicity evaluation in Sprague-Dawley rats: skin site and sex differences in sensitivity to drug-induced phototoxicity
