Elsevier

Psychiatry Research

Volume 225, Issues 1–2, 30 January 2015, Pages 31-39
Psychiatry Research

Pharmacological blockade of memory reconsolidation in posttraumatic stress disorder: Three negative psychophysiological studies

https://doi.org/10.1016/j.psychres.2014.09.005Get rights and content

Highlights

  • Reactivated memories must be restabilized (reconsolidated) if they are to persist.

  • d-cycloserine may facilitate memory destabilization.

  • Propranolol and mifepristone may block memory reconsolidation.

  • Here we failed to find pharmacological blockade of traumatic memory reconsolidation.

  • Possible reasons for this failure are discussed.

Abstract

Posttraumatic stress disorder (PTSD) may involve over-consolidated emotional memories of the traumatic event. Reactivation (RP) can return a memory to an unstable state, from which it must be restabilized (reconsolidated) if it is to persist. Pharmacological agents administered while the memory is unstable have been shown to impair reconsolidation. The N-methyl-d-aspartate (NMDA) partial agonist d-cycloserine (DCS) may promote memory destabilization. In the three studies reported here, we investigated whether the β-adrenergic blocker propranolol or the glucocorticoid (GR) antagonist mifepristone, given at the time of traumatic memory reactivation, could reduce PTSD symptoms and physiological responding during subsequent traumatic imagery. Individuals with PTSD were randomized as follows: Study One: propranolol with memory reactivation (n=10) or without reactivation (n=8); Study Two: reactivation mifepristone (n=13), non-reactivation (NRP) mifepristone (n=15), or double placebo (PL) (n=15); Study Three: reactivation mifepristone plus d-cycloserine (n=16), or two placebos (n=15). Subjects underwent memory retrieval by describing their traumatic event. A week later they engaged in script-driven traumatic mental imagery, while heart rate (HR), skin conductance (SC), and facial electromyogram (EMG) responses were measured. There were no significant group differences in physiological responsivity or change in PTSD symptoms in any of the studies. These results do not support successful blockade of reconsolidation of traumatic memories in PTSD.

Section snippets

General introduction

Animal research suggests that under favorable conditions, the retrieval (reactivation (RP)) of a consolidated memory may return it to a labile state from which it must be restabilized in order to persist (Nader et al., 2000). This restabilization process is termed reconsolidation. It involves neurobiological mechanisms that are similar but not identical to those involved in memory consolidation (Lee et al., 2004). Reconsolidation is largely demonstrated by its blockade. It derives its support

General discussion

Study One aimed to replicate and extend earlier findings that propranolol accompanying traumatic memory reactivation weakens physiological responding during subsequent mental imagery of the traumatic event (Brunet et al., 2008). Studies Two and Three pursued novel pharmacological interventions for traumatic memory reconsolidation blockade, specifically mifepristone alone or in combination with DCS. Unfortunately, the results of all three studies failed to show significant effects of

Conflict of interest

None of the authors have competing interests.

Acknowledgments

This study was funded by U.S. Army grant # W81XWH-08-2-0126.

Roy Karnovsky at Danco Laboratories provided the mifepristone medication. Dr. Anna Ruef and Ms. Heike Croteau provided valuable assistance.

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    Each contributed equally to this work.

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