Despite substantial therapeutic advances, Posttraumatic Stress Disorder (PTSD) remains
difficult to treat. One promising new area of research is in post-reactivation pharmacologic
intervention, which is based upon the concept of blockade of memory reconsolidation. Recent
animal research suggests that reactivation (retrieval) of a stored memory can return it to a
labile (alterable) state from which it must be restabilized in order to persist. This process
is called "reconsolidation," and various drugs have been found to block it in animals. This
blockade may lead to a weakening of the original memory trace.
The aim of this study is to pilot the effect of mifepristone on physiologic responding during
traumatic imagery. Although mifepristone is widely and safely used to cause a medical
abortion, it is also a powerful stress hormone receptor blocker. These stress hormones,
called glucocorticoids, may enhance memory (re)consolidation. Indeed, a recent study in
animals reported that mifepristone blocked reconsolidation of context-conditioned fear in
rats.
Reconsolidation blockade is a two-stage process. First, the memory must be destabilized by
recalling it. Second, reconsolidation of the memory must be blocked by a drug. Memory traces
formed under stressful conditions may resist destabilization and thus are inaccessible to
reconsolidation blockers. However, when a reconsolidation blocker was paired with
d-cycloserine (DCS) in animals that had been trained under stressful conditions,
reconsolidation blockade became successful. These results suggest that DCS promotes the
destabilization of resistant memory traces. The traumatic memories of individuals with PTSD
may be particularly resistant to destabilization. Therefore, this study will compare
mifepristone paired with DCS to placebo controls.
The same script-driven traumatic imagery method validated in previous studies of propranolol
in this lab will be used. Briefly, subjects with PTSD will describe their traumatic event
during a script preparation session, which will reactivate the memory. They will then receive
a) mifepristone and DCS or b) placebo. A week later, they will engage in script-driven mental
imagery of their traumatic event while physiologic responses (heart rate, sweating, etc) are
measured. This is a pilot study so there are no formal hypotheses. The aim is to estimate
effect sizes for mifepristone and to compare them with effect sizes for propranolol from this
lab's previous work.