Effect of post-retrieval propranolol on psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder

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Abstract

The β-adrenergic blocker propranolol given within hours of a psychologically traumatic event reduces physiologic responses during subsequent mental imagery of the event. Here we tested the effect of propranolol given after the retrieval of memories of past traumatic events. Subjects with chronic post-traumatic stress disorder described their traumatic event during a script preparation session and then received a one-day dose of propranolol (n = 9) or placebo (n = 10), randomized and double-blind. A week later, they engaged in script-driven mental imagery of their traumatic event while heart rate, skin conductance, and left corrugator electromyogram were measured. Physiologic responses were significantly smaller in the subjects who had received post-reactivation propranolol a week earlier. Propranolol given after reactivation of the memory of a past traumatic event reduces physiologic responding during subsequent mental imagery of the event in a similar manner to propranolol given shortly after the occurrence of a traumatic event.

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Objectives

According to a translational model of post-traumatic stress disorder (PTSD) based upon hormonal modulation of Pavlovian conditioning (Pitman, 1989), a terrifying event (unconditioned stimulus, UCS) overstimulates stress hormones as part of an unconditioned fear response (UCR). These hormones overly strengthen the consolidation of conditioned fear, which is later manifest in durable fear responses (conditioned responses, CRs) to reminders of the event (conditioned stimuli, CSs). Animal and human

Materials and methods

Exclusion criteria included (a) systolic blood pressure (SBP) <100 mm Hg; (b) asthma, heart failure, heart block, certain cardiac arrhythmias, or insulin-requiring diabetes; (c) previous adverse reaction to a β-blocker; (d) use of another β-blocker; (e) use of medication that could involve potentially dangerous interactions with propranolol; (f) pregnant or breast feeding; (g) “recovered” memory of traumatic event; or (h) dissociative experiences scale (Bernstein and Putnam, 1986) score >20.

Results

Overall physiologic responding during mental imagery of the traumatic event was significantly smaller in the PTSD subjects who had received propranolol a week earlier compared to those who had received placebo (F(3, 15) = 5.1; p = 0.007; η2 = 0.49). Univariate analyses indicated that HR and SC, but not EMG, responses were significantly smaller in the propranolol compared to the placebo subjects (Fig. 1). The mean HR and SC responses of the placebo subjects were above the normative cut-offs for PTSD,

Discussion

A comparison of the results of the present study with those of a previous study in which propranolol was administered acutely post-trauma (Pitman et al., 2002) reveals that propranolol given after the occurrence of a traumatic event and propranolol given after retrieval of the memory of a past traumatic event similarly reduce physiologic responding during subsequent mental imagery of the event. In the present study, the PTSD subjects who received post-retrieval placebo showed physiologic

Acknowledgements

We thank Marianne Smiley and Heike Croteau for technical assistance. This study was supported by the Fonds de recherche en senté du Quebec (AB); Fondation EJLB, Alfred P. Sloan Foundation, Natural Sciences and Engineering Research Council of Canada, Volkswagen Foundation, and Canadian Institutes for Health Research (KN); a US VA Medical Research Service Merit Review Grant (SPO); and USPHS Grant MH068603 (RKP). None of the sponsors had any role in study design; in the collection, analysis and

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Cited by (0)

Drs. Brunet, Nader, and Pitman designed the study. Drs. Brunet and Pitman wrote the protocol. Dr. Tremblay served as study physician. Ms. Robertson served as study coordinator and data manager. Dr. Orr performed the statistical analyses. Drs. Brunet and Pitman wrote the first draft of the manuscript. All authors contributed to and have approved the final manuscript.

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