Revisiting propranolol and PTSD: Memory erasure or extinction enhancement? - PubMed (original) (raw)
Review
Revisiting propranolol and PTSD: Memory erasure or extinction enhancement?
Thomas F Giustino et al. Neurobiol Learn Mem. 2016 Apr.
Abstract
Posttraumatic stress disorder (PTSD) has been described as the only neuropsychiatric disorder with a known cause, yet effective behavioral and pharmacotherapies remain elusive for many afflicted individuals. PTSD is characterized by heightened noradrenergic signaling, as well as a resistance to extinction learning. Research aimed at promoting more effective treatment of PTSD has focused on memory erasure (disrupting reconsolidation) and/or enhancing extinction retention through pharmacological manipulations. Propranolol, a β-adrenoceptor antagonist, has received considerable attention for its therapeutic potential in PTSD, although its impact on patients is not always effective. In this review, we briefly examine the consequences of β-noradrenergic manipulations on both reconsolidation and extinction learning in rodents and in humans. We suggest that propranolol is effective as a fear-reducing agent when paired with behavioral therapy soon after trauma when psychological stress is high, possibly preventing or dampening the later development of PTSD. In individuals who have already suffered from PTSD for a significant period of time, propranolol may be less effective at disrupting reconsolidation of strong fear memories. Also, when PTSD has already developed, chronic treatment with propranolol may be more effective than acute intervention, given that individuals with PTSD tend to experience long-term, elevated noradrenergic hyperarousal.
Keywords: Consolidation; Extinction; Fear; Norepinephrine; PTSD; Propranolol; Reconsolidation.
Copyright © 2016 Elsevier Inc. All rights reserved.
Conflict of interest statement
Conflicts of Interest
None declared.
Figures
Figure 1
Schematic representation showing the effect of post-reactivation propranolol on reconsolidation. In rodents, conditioning typically consists of a single CS-US pairing (left). The next day animals receive 1 CS reactivation trial, immediately followed by propranolol or vehicle administration (middle). When tested at later time points in the absence of drug, propranolol treated animals show reduced fear responding (right). Abbreviations: baseline period (BL), injection (INJ), vehicle (Veh), propranolol (Prop).
Figure 2
Schematic data showing the bi-directional effect of propranolol treatment on extinction learning at different time points. a) Animals are typically conditioned with several CS-US pairings (left). In an immediate extinction procedure, animals received either vehicle or propranolol 30 min prior to extinction training (and immediately after conditioning). Propranolol treatment reduced elevated baseline levels of freezing and attenuated fear throughout the session (middle). When tested for extinction recall later (in a drug free state), prior propranolol treatment significantly reduced the spontaneous recovery of fear, ameliorating the immediate extinction deficit (right). b) Similar to animals undergoing immediate extinction procedures, “no-extinction” controls received vehicle or propranolol immediately following conditioning, but were exposed to the extinction context in the absence of CS presentation. Propranolol reduced elevated levels of baseline freezing, although no difference was observed between groups throughout the session (middle). Upon test, animals froze at similarly high levels (right). c) In delayed extinction, animals were conditioned using the same protocol as in a and b. However, animals were returned to their home cage following conditioning and not injected. The following day, rats received vehicle or propranolol administration 30 min prior to an extinction session. No differences were observed at baseline or during tone presentation (middle). When tested for extinction recall (in a drug free state), prior propranolol treatment impaired retrieval relative to vehicle controls (right). Abbreviations as in Figure 1 legend. Data are adapted from Fitzgerald et al. (2015).
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