Limited efficacy of propranolol on the reconsolidation of fear memories

Abstract

Previous studies suggested that the b-adrenergic receptor antagonist propranolol might be a novel, potential treatment for post-traumatic stress disorder (PTSD). This hypothesis stemmed mainly from rodent studies showing that propranolol interferes with the reconsolidation of Pavlovian fear conditioning (FC). However, subsequent investigations in humans have produced controversial evidence about the effect of propranolol on fear memories and an effect on PTSD symptomatology has yet to be reported. Thus, it remains to be established whether propranolol interferes with the reconsolidation of fear memories at large. To address this question, we tested the effect of systemic injections of propranolol administered before or after the retrieval of an inhibitory avoidance (IA) memory elicited with different footshock intensities. In parallel, the same treatment was tested on the reconsolidation of Pavlovian FC. Propranolol showed no effect on the reconsolidation of IA, although the pre-retrieval administration resulted in a significant retrieval impairment. This impairment was transient, and memory returned to control levels at later times. In agreement with previous studies, we found that systemic administration of propranolol disrupts the reconsolidation of Pavlovian FC and that its injection following a retrieval elicited by cue exposure also interferes with the reconsolidation of contextual FC. Hence, propranolol disrupts the reconsolidation of Pavlovian FC, but has no effect on the reconsolidation of IA. The results indicate that the efficacy of systemic administration of propranol in disrupting the reconsolidation of fear memories is limited.

Developing Memory Reconsolidation Blockers as Novel PTSD Treatments

“…This negative result is partially at odds with results of some previously published studies that used the same 10 mg/kg dose as in the present study (Debiec & Ledoux, 2004;Muravieva & Alberini, 2010;Przybyslawski et al, 1999) or nearly the same dose (5 mg/kg; Abrari et al, 2008). The discrepancy might be explained by design and methodological differences.…”

“…Interestingly, in the last of the two above studies (Muravieva & Alberini, 2010), propranolol failed to block the reconsolidation of inhibitory avoidance, whereas systemic mifepristone had previously succeeded in doing so in a study in the same laboratory . In addition to the present results, this suggests that, compared to propranolol, mifepristone may be a superior reconsolidation blocker of conditioned fear across various designs and may ultimately turn out to be a more useful treatment Figure 2.…”

“…The reconsolidation process has mainly been revealed through its blockade. When certain drugs are administered shortly after reactivation, subsequent testing finds the memory to be diminished (Abrari, Rashidy-Pour, Semnanian, & Fathollahi, 2008;Debiec & Ledoux, 2004;Jin, Lu, Yang, Ma, & Li, 2007;Muravieva & Alberini, 2010;Nader, Schafe, & Le Doux, 2000;Przybyslawski, Roullet, & Sara, 1999;.…”

“…The present study used a cue-conditioning procedure whereas one of these previous positive studies employed inhibitory avoidance (Przybyslawski et al, 1999) and one employed context conditioning (Abrari et al, 2008). Of the two studies reporting that propranolol blocked reconsolidation of cue conditioning, one (Muravieva & Alberini, 2010) used Long Evans, rather than Sprague-Dawley rats as herein. In both cueconditioning studies (Debiec & Ledoux, 2004;Muravieva & Alberini, 2010), the conditioned responses were acquired in one experimental chamber (context), but reactivated and then tested in another chamber.…”

“…Of the two studies reporting that propranolol blocked reconsolidation of cue conditioning, one (Muravieva & Alberini, 2010) used Long Evans, rather than Sprague-Dawley rats as herein. In both cueconditioning studies (Debiec & Ledoux, 2004;Muravieva & Alberini, 2010), the conditioned responses were acquired in one experimental chamber (context), but reactivated and then tested in another chamber. For reasons of clinical applicability described above, in the present study all procedures were performed in the same chamber.…”