Can fear extinction be enhanced? A review of pharmacological and behavioral findings

Abstract

There is considerable interest, from both a basic and clinical standpoint, in gaining a greater understanding of how pharmaceutical or behavioral manipulations alter fear extinction in animals. Not only does fear extinction in rodents model exposure therapy in humans, where the latter is a cornerstone of behavioral intervention for anxiety disorders such as post-traumatic stress disorder and specific phobias, but also understanding more about extinction provides basic information into learning and memory processes and their underlying circuitry. In this paper, we briefly review three principal approaches that have been used to modulate extinction processes in animals and humans: a purely pharmacological approach, the more widespread approach of combining pharmacology with behavior, and a purely behavioral approach. The pharmacological studies comprise modulation by: brain derived neurotrophic factor (BDNF), d-cycloserine, serotonergic and noradrenergic drugs, neuropeptides, endocannabinoids, glucocorticoids, histone deacetylase (HDAC) inhibitors, and others. These studies strongly suggest that extinction can be modulated by drugs, behavioral interventions, or their combination, although not always in a lasting manner. We suggest that pharmacotherapeutic manipulations provide considerable promise for promoting effective and lasting fear reduction in individuals with anxiety disorders.

Intensive prolonged exposure therapy for chronic PTSD patients following multiple trauma and multiple treatment attempts

“…Additionally or alternatively, the improvement in this subgroup might not necessarily result from the added exposure but rather from the spacing of the additional exposure sessions during the booster phase. Animal studies (see Fitzgerald et al, 2014) showed that, once initiated in a massed way, extinction learning is boosted when subsequent trials are spaced (Cain et al, 2003). Third, the patients in this cluster may have needed exposure in a variety of contexts such as the home environment.…”

“…More theoretically, results from animal studies about fear extinction learning (i.e. the development of new associations with the stimulus that inhibits the manifestation of the original fear memory and the presumed mechanism of action of exposure therapy; see for an overview Fitzgerald, Seemann, & Maren, 2014) showed that once extinction learning is initiated in a massed way, further extinction learning is more effective when trials are spaced (Cain, Blouin, & Barad, 2003). …”

State anxiety modulates the return of fear

“…A major limitation to long-term remission of anxiety disorders is the high relapse rate despite of effective psychological and pharmacological interventions (Yonkers, Bruce, Dyck, & Keller, 2003). Thus, relapse prevention may represent a good intervention point for improving long-term therapeutic efficacy, which has recently become a major focus of experimental and clinical research (Fitzgerald, Seemann, & Maren, 2014;Haaker et al, 2013;Kindt, Soeter, & Vervliet, 2009;Schiller et al, 2010).…”

Noradrenergic blockade stabilizes prefrontal activity and enables fear extinction under stress

“…Moreover, an inability to suppress or extinguish fear memories may sustain pathologically high levels of fear in patients with PTSD years after the trauma (1)(2)(3)(4)(5)(6). A variety of clinical interventions to facilitate fear extinction in patients with PTSD are currently being explored, although effective treatment for many afflicted individuals remains elusive (7,8).…”