Metyrapone Administration Reduces the Strength of an Emotional Memory Trace in a Long-Lasting Manner

Context: It has recently been demonstrated that the process of memory retrieval serves as a reactivation mechanism whereby the memory trace that is reactivated during retrieval is once again sensitive to modifications by environmental or pharmacological manipulations. Recent studies have shown that glucocorticoids (GCs) have the capacity to modulate the process of memory retrieval. This suggests that GCs could be an interesting avenue to investigate with regard to reduction of emotional memory. Objective: The current study assessed whether a pharmacological decrease in GC levels, induced by metyrapone, a potent inhibitor of GC secretion, would affect retrieval of emotional and neutral information in an acute and/or long-lasting manner. Design, Setting, Participants, and Intervention: To do so, 1 X 750 mg dose of metyrapone, 2 X 750 mg dose of metyrapone, or placebo was administered to young normal participants 3 d after the encoding of a slide show having neutral and emotional segments. The experiment took place in a university and a hospital setting. Main Outcome Measure: Memory performance was assessed after treatment and 4 d later. Results: Results showed that retrieval of emotional information was acutely impaired in the double-dose metyrapone group and that this effect was still present 4 d later, when GC levels were not different between groups. Conclusions: These results show that decreasing GC levels via metyrapone administration is an efficient way to reduce the strength of an emotional memory in a long-lasting manner. (J Clin Endocrinol Metab 96: E1221-E1227, 2011)