Acute but not permanent effects of propranolol on fear memory expression in humans

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Experimental evidence in humans and non-human animals suggests that the administration of propranolol shortly after the retrieval of an emotional memory can lead to an attenuation of its later expression, a phenomenon known as post-reactivation amnesia. Using more potent amnestic drugs, post-reactivation amnesia has been shown in animals to be reversible by re-administration of the drug prior to memory retention testing. The latter finding suggests that, at least under some circumstances, post-reactivation amnesia may not reflect a disruption of reconsolidation (i.e., a memory storage deficit) but an acquired state-dependency of memory expression (i.e., a memory retrieval deficit that is relieved when the drug state is recreated during testing). We conducted a double-blind, placebo-controlled study to investigate whether the previously established amnestic effects of post-reactivation propranolol administration on memory retention in humans may similarly reflect a retrieval deficit. In four groups of participants, fear memories were first established through differential fear conditioning. One day later, a single presentation of the CS+ without shock was used to reactivate the memory in three of the four groups, followed by the administration of 40 mg Propranolol HCl (Groups PrPl and PrPr) or placebo (Group PlPl). Memory was not reactivated in the fourth group (Group NR). Another 24 h later, Propranolol HCl (Group PrPr) or placebo (Groups PrPl, PlPl, and NR) was again administered, followed by a test of memory retention (extinction testing) and recovery (reinstatement testing). We did not observe any effects of post-reactivation propranolol on memory retention; conditioned responding was similar for all groups at the start of retention testing and similarly sensitive to recovery through reinstatement. We did observe an acute effect of propranolol administration on fear-potentiated startle responding during retention testing in Group PrPr, where participants exhibited attenuated startle responses during extinction testing but similar sensitivity to reinstatement as participants in the other groups. While our findings fail to corroborate previous reports of propranolol-induced post-reactivation amnesia in humans, they do point to acute effects of propranolol administration on extinction performance.




Chalkia, A., Weermeijer, J., Van Oudenhove, L., & Beckers, T. (2019). Acute but not permanent effects of propranolol on fear memory expression in humans. Frontiers in Human Neuroscience, 13.

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