Glucocorticoid-induced enhancement of extinction—from animal models to clinical trials

Abstract

Extensive evidence from both animal model and human research indicates that glucocorticoid hormones are crucially involved in modulating memory performance. Glucocorticoids, which are released during stressful or emotionally arousing experiences, enhance the consolidation of new memories, including extinction memory, but reduce the retrieval of previously stored memories. These memory-modulating properties of glucocorticoids have recently received considerable interest for translational purposes because strong aversive memories lie at the core of several fear-related disorders, including post-traumatic stress disorder and phobias. Moreover, exposure-based psychological treatment of these disorders relies on successful fear extinction. In this review, we argue that glucocorticoid-based interventions facilitate fear extinction by reducing the retrieval of aversive memories and enhancing the consolidation of extinction memories. Several clinical trials have already indicated that glucocorticoids might be indeed helpful in the treatment of fear-related disorders.

Lest we forget: towards therapeutic amnesia

“…But glucocorticoids impair recall of information already 'downloaded' to longterm memory. 5 These and other observations suggest that the processes underlying the three types of memory are independent, running in parallel rather than sequentially. 7 The slow consolidation into long-term memory seems to allow the brain to alter the strength of the recollection depending on the event's importance.…”

“…2 This offers the opportunity to interrupt the cycle of involuntary recollection, re-experiencing and reconsolidation of traumatic memories that underlies PTSD and phobias. 5 The liability of reactivated traumatic memories also means that 'fabricated' details can become part of the recalled narrative, which the person believes is true. One study, for example, interviewed 2641 people exposed to the 9/11 attack and the restoration of the World Trade Center between May 2002 and September 2004.…”

“…8 Experiences that arouse emotion or cause stress also tend to be well remembered. 5,7 On the other hand, stress and emotion can hinder recall of previous events. 5 Insights into the biological basis of these observations offer another promising approach to therapeutic amnesia.…”

“…1 Exposure therapy -the usual treatment for intrusive, involuntary recollections -does not seem to reverse or remove memories. 4,5 Rather, exposure therapy aims at extinguishing the conditioned fear response associated with the memory. Exposure therapy, however, seems to be effective in only about half of patients.…”

“…Exposure therapy, however, seems to be effective in only about half of patients. 5 So, many researchers are investigating pharmacological approaches that promote 'therapeutic forgetting'. 2 A common problem Despite our civilised veneer, life remains surprisingly nasty and brutish.…”