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

Neurobiol Learn Mem. 2019 Dec:166:107105. doi: 10.1016/j.nlm.2019.107105. Epub 2019 Nov 6.

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.

Keywords: Contextual fear memory; Midazolam; Post-reactivation amnesia; Propranolol; Rats; Reconsolidation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amnesia / chemically induced*
  • Animals
  • Conditioning, Psychological
  • Fear / drug effects*
  • Hypnotics and Sedatives / administration & dosage*
  • Mental Recall / drug effects*
  • Midazolam / administration & dosage*
  • Propranolol / administration & dosage*
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Reproducibility of Results

Substances

  • Hypnotics and Sedatives
  • Propranolol
  • Midazolam